Anxiolytic-Like Property of Risperidone and Olanzapine as Examined in Multiple Measures of Fear in Rats

Atypical antipsychotics are also used in the treatment of anxiety-related disorders. Clinical and preclinical evidence regarding their intrinsic anxiolytic efficacy has been mixed. In this study, we examined the potential anxiolytic-like effects of risperidone and olanzapine, and compared them with haloperidol, chlordiazepoxide (a prototype of sedative–anxiolytic drug) or citalopram (a selective serotonin reuptake inhibitor). We used a composite of two-way avoidance conditioning and acoustic startle reflex model and examined the effects of drug treatments during the acquisition phase (Experiment 1) or extinction phase (Experiments 2 and 3) on multiple measures of conditioned and unconditioned fear/anxiety-like responses. In Experiment 4, we further compared risperidone, olanzapine, haloperidol, citalopram and chlordiazepoxide in a standard elevated plus maze test. Results revealed three distinct anxiolytic-like profiles associated with risperidone, olanzapine and chlordiazepoxide. Risperidone, especially at 1.0 mg/kg, significantly decreased the number of avoidance responses, 22 kHz ultrasonic vocalization, avoidance conditioning-induced hyperthermia and startle reactivity, but did not affect defecations or time spent on the open arms. Olanzapine (2.0 mg/kg, sc) significantly decreased the number of avoidance responses, 22 kHz vocalization and amount of defecations, but it did not inhibit startle reactivity and time spent on the open arms. Chlordiazepoxide (10 mg/kg, ip) significantly decreased the number of 22 kHz vocalization, avoidance conditioning-induced hyperthermia and amount of defecations, and increased time spent on the open arms, but did not decrease avoidance responses or startle reactivity. Haloperidol and citalopram did not display any anxiolytic-like property in these tests. The results highlight the importance of using multiple measures of fear-related responses to delineate behavioral profiles of psychotherapeutic drugs.

Metabolismus von Psychopharmaka durch das Cytochrom P450-Enzymsystem im Alter

Altern geht mit einer Reihe physiologischer Veränderungen einher. Da in höherem Lebensalter überdurchschnittlich viele Arzneistoffe eingenommen werden und häufig mehrere Erkrankungen gleichzeitig vorliegen, können Auffälligkeiten in den Arzneimittelkonzentrationen im Blut nicht nur altersbedingt, sondern auch krankheitsbedingt oder durch Arzneimittelwechselwirkungen verursacht sein.rnrnDie vorliegende Arbeit untersucht die Fragestellung, ob der Arzneimittelmetabolismus bei Alterspatenten generell, oder nur bei Patienten mit Multimorbidität und –medikation verändert ist, und in welchem Lebensalter diese Veränderungen einsetzen. Im Mittelpunkt stand dabei die Frage, ob die Aktivitäten distinkter Arzneimittel-abbauender Enzyme der Cytochrom P450-Enzym-Familie (CYP) verändert sind. Da viele Psychopharmaka nur bei Patienten im Alter zwischen 18 und 65 Jahren zugelassen sind, wurde die Hypothese geprüft, dass sich Patienten im Alter über und unter 65 Jahren in ihren Medikamentenspiegeln unterscheiden.rnrnFür die Untersuchungen wurde eine Datenbank aus Blutspiegelmessungen erstellt, die im Rahmen des pharmakotherapiebegleitenden TDM erhoben worden waren. Die Blutspiegel stammten von insgesamt 4197 Patienten, die mit Amisulprid, Aripiprazol, Citalopram, Clozapin, Donepezil, Escitalopram, Mirtazapin, Quetiapin, Risperidon, Sertralin, Venlafaxin oder Ziprasidon behandelt wurden. Die Messungen wurden ergänzt mit Angaben aus den TDM-Anforderungsscheinen bezüglich Tagesdosis, Begleitmedikamenten, Schweregrad der Erkrankung, Therapieerfolg und Verträglichkeit der Medikation. Zusätzlich wurden klinische Befunde der Leber- und Nierenfunktion einbezogen, sowie Angaben zur Berechnung des BMI. Die in vivo-CYP-Enzymaktivitäten wurden anhand von metabolischen Ratios (Serumkonzentrationen Metabolit/ Serumkonzentration Muttersubstanz) beurteilt.rnrnIm Mittel stieg der Schweregrad der Erkrankung mit dem Alter und der Therapieerfolg verschlechterte sich. Dies betraf im Einzelnen nur Patienten, die mit Amisulprid oder Clozapin behandelt worden waren. Ältere Patienten litten häufiger an Nebenwirkungen als jüngere.rnUnter Aripiprazol, Quetiapin, Sertralin und Venlafaxin erreichten Alterspatienten mit niedrigeren Tagesdosen gleiche Therapieerfolge wie jüngere Patienten.rnPatienten, die mit Clozapin oder Amisulprid behandelt wurden, zeigten im Alter schlechtere Behandlungserfolge bei gleicher (Clozapin) bzw. niedrigerer (Amisulprid) Tagesdosis.rnTherapieerfolg und mittlere Tagesdosis änderten sich bei Patienten, die Ziprasidon, Donepezil, Citalopram, Escitalopram und Mirtazapin einnahmen, nicht altersabhängig.rnrnAltersabhängige Unterschiede der Serumspiegel zeigten sich für Amisulprid, Aripiprazol, Donepezil, Mirtazapin, Desmethylmirtazapin, Quetiapin und DesmethylsertralinrnAllerdings lagen die Altersgrenzen außer bei Donepezil deutlich niedriger als die gängig angenommene, nämlich bei 35 Jahren (Aripiprazol), 70 Jahren (Donepezil), 55 Jahren (D-Sertralin), 41 Jahren (Amisulprid), 49 Jahren (Quetiapin) und 58 Jahren (Mirtazapin).rnEs bestand kein Zusammenhang zwischen dem Auftreten veränderter Serumspiegel im Alter und dem Verteilungsvolumen, der Plasmaproteinbindung oder der Eliminationshalbwertszeit der untersuchten Wirkstoffe.rnrnBei Patienten ohne Comedikation fand sich in keinem Fall eine altersabhängige Veränderung der Ratio. Es ergab sich daher kein Hinweis auf eine Veränderung der CYP-Aktivität im Alter. Die Einnahme von Comedikation nahm mit dem Alter zu, hierfür ließ sich eine Altersgrenze von 49 Jahren definieren. Unter Polytherapie wurden Veränderungen der CYP-Aktivität beobachtet.rnrnDer Einfluss veränderter Leber- oder Nierenfunktion auf die Biotransformation von Pharmaka wurde anhand von Serumspiegeln von Patienten, die mit Donepezil, Venlafaxin, Citalopram oder Escitalopram behandelt wurden, untersucht. rnBei keinem Wirkstoff wurden unter auffälligen Leber- oder Nierenparametern signifikant veränderte Serumspiegel gemessen.rnEine Abhängigkeit der Serumspiegel vom Körpergewicht wurde nur für Desmethylsertralin gefunden. Die Spiegel waren bei Patienten mit einem Body Mass Index unter 20 signifikant höher als bei Patienten mit einem Index über 20. Aufgrund der kleinen Fallgruppe und der Tatsache, dass der Serumspiegel der Muttersubstanz nicht stieg, konnte nicht zwingend von einem Alterseinfluss aufgrund der veränderten Körperzusammensetzung ausgegangen werden.rnInsgesamt ergaben sich aus den Untersuchungen Hinweise auf moderate altersabhängige Veränderungen der Pharmakokinetik. Es ließen sich allerdings keine allgemeinen Dosierempfehlungen für Alterspatienten ableiten. Es zeigte sich jedoch, dass mit altersabhängigen Veränderungen der Pharmakokinetik bereits nach dem 50. Lebensjahr zu rechnen ist. Weitere Untersuchungen sollten auch den Alterseffekt auf gastrointestinale Transporter einbeziehen, die die aktive Aufnahme von Arzneistoffen ins Blut bewerkstelligen. Unklar ist auch die Rolle des Alterns auf die Aktivität des P-Glykoproteins. rn

Screening for drugs in oral fluid : illicit drug use and drug driving in a sample of urban and regional Queensland motorists

Police services in a number of Australian states and overseas jurisdictions have begun to implement or consider random road-side drug testing of drivers. This paper outlines research conducted to provide an estimate of the extent of drug driving in a sample of Queensland drivers in regional, rural and metropolitan areas. Oral fluid samples were collected from 2657 Queensland motorists and screened for illicit substances including cannabis (delta 9 tetrahydrocannibinol [THC]), amphetamines, ecstasy, and cocaine. Overall, 3.8% of the sample (n = 101) screened positive for at least one illicit substance, although multiple drugs were identified in a sample of 23 respondents. The most common drugs detected in oral fluid were ecstasy (n = 53), and cannabis (n = 46) followed by amphetamines (n = 23). A key finding was that cannabis was confirmed as the most common self-reported drug combined with driving and that individuals who tested positive to any drug through oral fluid analysis were also more likely to report the highest frequency of drug driving. Furthermore, a comparison between drug vs. drink driving detection rates for one region of the study, revealed a higher detection rate for drug driving (3.8%) vs. drink driving (0.8%). This research provides evidence that drug driving is relatively prevalent on Queensland roads, and may in fact be more common than drink driving. This paper will further outline the study findings’ and present possible directions for future drug driving research.

Alcohol and other drugs in the Australian construction industry : A national evaluation and the best way forward

Anecdotal evidence highlights issues of alcohol and other drugs (AODs) and its association with safety risk on construction sites. Information is limited however regarding the prevalence of AODs in the workplace and there is limited evidential guidance regarding how to effectively address it. This research aimed to scientifically evaluate the use of AODs within the Australian construction industry in order to reduce the potential resulting safety and performance impacts and engender a cultural change in the workforce. A national qualitative and quantitative evaluation of the use of AODs was conducted with approximately 500 employees. Results indicate that as in the general population, a proportion of those sampled in the construction sector may be at risk of hazardous alcohol consumption and support the need for evidence-based, tailored responses. This is the first known study to scientifically evaluate the use of AODs and potential workplace safety impacts in the construction sector.

New findings with old drugs for osteoporosis

Background : Postmenopausal osteoporosis is common and is associated with stooped posture, loss of height, back pain and fractures. Objectives/methods : This evaluation is of clinical outcome trials with tibolone (Long-Term Intervention of Fractures with Tibolone) and strontium ranelate (Spinal Osteoporosis Therapeutic Intervention) in postmenopausal osteoporosis. Results : Although the Long-Term Intervention of Fractures with Tibolone trial established that tibolone decreased the incidence of vertebral and non-vertebral fractures in postmenopausal osteoporosis, it also showed that tibolone caused a small increase in the incidence of stoke. The Spinal Osteoporosis Therapeutic Intervention trial established that strontium ranelate decreased the incidence of vertebral fractures, but had little effect on the incidence of non-vertebral fractures. Conclusions : As some of the bisphosphonates (alendronate, risedronate, zoledronic acid) have been shown to prevent hip fractures without increasing the incidence of stroke, they should be preferred to tibolone and strontium in the treatment of postmenopausal osteoporosis.

Safeguarding rural Australia : addressing masculinity and violence in rural settings. Data report No. 4 - Risky behaviour - misuse of alcohol, illicit drugs, firearms use and abuse, other risky behaviour

This report focuses on our examination of extant data which have been sourced with respect to personally and socially risky behaviour associated with males living in regional and remote Australia . The AIHW (2008: PHE 97:89) defines personally risky behaviour, on the one hand, as working, swimming, boating, driving or operating hazardous machinery while intoxicated with alcohol or an illicit drug. Socially risky behaviour, on the other hand, is defined as creating a public disturbance, damaging property, stealing or verbally or physically abusing someone while intoxicated with alcohol or an illicit drug. Additional commentary resulting from exploration, examination and analyses of secondary data is published online in complementary reports in this series.

Drugs, dental professionals and the law

Dentists have the privilege of possessing, administering and prescribing drugs, including highly addictive medications, to their patients. But because drugs are often vulnerable to being abused by all members of society, including dentists and their patients, and because drugs can be dangerous, they are tightly regulated in Canada by the federal and provincial/territorial governments. Regulatory and professional dental bodies also provide guidance for their members about how to best administer and prescribe drugs. This chapter outlines the regulation by federal and provincial/territorial governments in this area, examines the professional practice requirements set out by regulatory/professional bodies and the issue of drug abuse by dental professional and patients. It is important to note from the outset that governmental and professional regulations, policies and practices differ from province to province and territory to territory. This chapter aims to alert dentists to possible legal and professional issues surrounding the possession, administration and prescription of drugs. For detailed specific information about regulation, policies, ethical standards and professional practice standards in Canada or their province/ territory, dentists should contact their insurer or professional association.

Safety impacts of alcohol and other drugs in the construction industry : a research methodology

Anecdotal evidence from the infrastructure and building sectors highlights issues of drugs and alcohol and its association with safety risk on construction sites. Operating machinery and mobile equipment, proximity to live traffic together with congested sites, electrical equipment and operating at heights conspire to accentuate the potential adverse impact of drugs and alcohol in the workplace. While most Australian jurisdictions have identified this as a critical safety issue, information is limited regarding the prevalence of alcohol and other drugs in the workplace and there is limited evidential guidance regarding how to effectively and efficiently address such an issue. No known study has scientifically evaluated the relationship between the use of drugs and alcohol and safety impacts in construction, and there has been only limited adoption of nationally coordinated strategies, supported by employers and employees to render it socially unacceptable to arrive at a construction workplace with impaired judgement from drugs and alcohol. A nationally consistent collaborative approach across the construction workforce - involving employers and employees; clients; unions; contractors and sub-contractors is required to engender a cultural change in the construction workforce – in a similar manner to the on-going initiative in securing a cultural change to drink-driving in our society where peer intervention and support is encouraged. This study has four key objectives. Firstly, using the standard World Health Organisation AUDIT, a national qualitative and quantitative assessment of the use of drugs and alcohol will be carried out. This will build upon similar studies carried out in the Australian energy and mining sectors. Secondly, the development of an appropriate industry policy will adopt a non-punitive and rehabilitative approach developed in consultation with employers and employees across the infrastructure and building sectors, with the aim it be adopted nationally for adoption at the construction workplace. Thirdly, an industry-specific cultural change management program will be developed through a nationally collaborative approach to reducing the risk of impaired performance on construction sites and increasing workers’ commitment to drugs and alcohol safety. Finally, an implementation plan will be developed from data gathered from both managers and construction employees. Such an approach stands to benefit not only occupational health and safety, through a greater understanding of the safety impacts of alcohol and other drugs at work, but also alcohol and drug use as a wider community health issue. This paper will provide an overview of the background and significance of the study as well as outlining the proposed methodology that will be used to evaluate the safety impacts of alcohol and other drugs in the construction industry.

Safety impacts of alcohol and other drugs in the construction industry : Preliminary findings

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Safety impacts of alcohol and other drugs in construction : a mid term report

Estimated 640,700 persons suffered a work-related injury or illness in 2009-2010 and 444 lost their lives as a result in 2008-2009, in Australia Very little is known about what proportion of accidents are directly attributable to the effects of AOD Anecdotal evidence highlights issues of AOD and its association with safety risk on construction sites

New drugs for the treatment of coronary artery syndromes

Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

Sex, drugs, and deterrence : applying Stafford and Warr’s reconceptualization of deterrence theory to drug driving across the genders

A consistent finding in the literature is that males report greater usage of drugs and subsequently greater amounts of drug driving. Research also suggests that vicarious influences may be more pertinent to males than to females. Utilising Stafford and Warr’s (1993) reconceptualization of deterrence theory, this study sought to determine if the relative deterrent impact of zero-tolerance drug driving laws is disparate between genders. A sample of motorists’ (N = 899) completed a self-report questionnaire assessing participants frequency of drug driving and personal and vicarious experiences with punishment and punishment avoidance. Results show that males were significantly more likely to report future intentions of drug driving. Additionally, vicarious experiences of punishment avoidance was a more influential predictor of future drug driving instances for males with personal experiences of punishment avoidance a more influential predictor for females. These findings can inform gender sensitive media campaigns and interventions for convicted drug drivers.

Pleasure Consuming Medicine : The Queer Politics of Drugs By Kane Race [Review]

The queer studies field works to deconstruct dominant western discourses which cast gay men as hedonistic partygoers. Concurrently it examines the real social ramifications for some gay men for whom partying, illegal drugs and casual sex is an everyday reality. Another reality of gay male culture is HIV/AIDS and the legal prescribed medicines which accompany these conditions. Pleasure Consuming Medicine: The Queer Politics of Drugs explores these realities and the discourses surrounding them. Exploring the embodiments of illegal and prescription drug users, this book problematises the binary between prescription medicine use, where drug use is configured as a matter of consumer choice, and 'illicit' drug use which is heavily policed and condemned. Returning to the gay community it reviews community approaches to safe sex and drug use, and individual practices, to demonstrate alternative approaches to condemning drug usage.

Pleasure Consuming Medicine : The Queer Politics of Drugs By Kane Race [Review]

The queer studies field works to deconstruct dominant western discourses which cast gay men as hedonistic partygoers. Concurrently it examines the real social ramifications for some gay men for whom partying, illegal drugs and casual sex is an everyday reality. Another reality of gay male culture is HIV/AIDS and the legal prescribed medicines which accompany these conditions. Pleasure Consuming Medicine: The Queer Politics of Drugs explores these realities and the discourses surrounding them. Exploring the embodiments of illegal and prescription drug users, this book problematises the binary between prescription medicine use, where drug use is configured as a matter of consumer choice, and 'illicit' drug use which is heavily policed and condemned. Returning to the gay community it reviews community approaches to safe sex and drug use, and individual practices, to demonstrate alternative approaches to condemning drug usage.