- Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder. [Journal Article]
- BDBipolar Disord 2018 Feb 16
- CONCLUSIONS: The incidence of subsequent long-term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z-drug polytherapy have the highest risk of becoming long-term users, suggesting that these treatments should be used restrictively.
- Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality. [Journal Article]
- JPJ Psychopharmacol 2018 Feb 01; :269881118754734
- The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005-2012. Data on...
The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005-2012. Data on suicide by self-poisoning were obtained from the Office for National Statistics, information on intentional non-fatal self-poisoning was derived from the Multicentre Study of Self-harm in England and data on prescriptions in general practice from the Clinical Practice Research Datalink. We used two indices of relative toxicity: fatal toxicity (the number of fatal self-poisonings relative to the number of individuals prescribed each drug) and case fatality (the number of fatal relative to non-fatal self-poisonings). Diazepam was the reference drug in all analyses. Temazepam was 10 times (95% confidence interval 5.48-18.99) and zopiclone/zolpidem nine times (95% confidence interval 5.01-16.65) more toxic in overdose than diazepam (fatal-toxicity index). Temazepam and zopiclone/zolpidem were 13 (95% confidence interval 6.97-24.41) and 12 (95% confidence interval 6.62-22.17) times more toxic than diazepam, respectively (case-fatality index). Differences in alcohol involvement between the drugs were unlikely to account for the findings. Overdoses of temazepam and zopiclone/zolpidem are considerably more likely to result in death than overdoses of diazepam. Practitioners need to exercise caution when prescribing these drugs, especially for individuals who may be at risk of self-harm, and also consider non-pharmacological options.
- GeneReviews® [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 ye...
Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 years; the clinical course is highly variable with parkinsonism as the initial presenting sign, overshadowed by dystonia as the disease progresses. Features of parkinsonism include resting tremor, bradykinesia, rigidity, postural instability, and severe shuffling gait. The dystonia develops focally, most commonly in the jaw, neck, trunk, and eyes, and less commonly in the limbs, tongue, pharynx, and larynx, the most characteristic being jaw dystonia often progressing to neck dystonia. Individuals with pure parkinsonism have non-disabling symptoms that are only slowly progressive; those who develop a combination of parkinsonism and dystonia can develop multifocal or generalized symptoms within a few years and die prematurely from pneumonia or intercurrent infections. Female carriers are mostly asymptomatic, though a small minority may manifest dystonia, parkinsonism, or chorea.
- Medical prescriptions falsified by the patients: a twelve-year national monitoring to assess prescription drug diversion. [Journal Article]
- FCFundam Clin Pharmacol 2018 Feb 13
- Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified ...
Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms and drugs. Description of the dataset in 3 periods (2001-2004, 2005-2008, and 2009-2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs. The 4469 falsified prescriptions concerned most often females (51.6%). Average age was 46.5 years. Zolpidem, bromazepam and buprenorphine were the most frequent drugs. Alone, 13 drugs (1.7%, 13/772) represented more than 40% of the total reports (3055/7272). They were associated with 3 diversion profiles: 1) buprenorphine, flunitrazepam, morphine were mentioned on overlapping secure prescription forms presented by young men; 2) alprazolam, bromazepam, zolpidem, codeine/acetaminophen were mentioned on simple prescription forms presented by experienced women; and 3) acetaminophen and lorazepam were mentioned on modified prescription forms presented by elderly subjects. Clonazepam, clorazepate, dextropropoxyphene, zopiclone moved between those profiles. The patterns of falsified prescriptions provided in this study contribute to enhance the scientific knowledge on the most diverted prescription drugs. The latter follow distinct trajectories across time depending on their pharmacology (including their abuse/addiction potential) and on their regulation's history. The close and continuous analysis of falsified prescriptions is an excellent way to monitor prescription drug diversion. This article is protected by copyright. All rights reserved.
- Sleep and Sedative States Induced by Targeting the Histamine and Noradrenergic Systems. [Review]
- FNFront Neural Circuits 2018; 12:4
- Sedatives target just a handful of receptors and ion channels. But we have no satisfying explanation for how activating these receptors produces sedation. In particular, do sedatives act at restricte...
Sedatives target just a handful of receptors and ion channels. But we have no satisfying explanation for how activating these receptors produces sedation. In particular, do sedatives act at restricted brain locations and circuitries or more widely? Two prominent sedative drugs in clinical use are zolpidem, a GABAAreceptor positive allosteric modulator, and dexmedetomidine (DEX), a selective α2 adrenergic receptor agonist. By targeting hypothalamic neuromodulatory systems both drugs induce a sleep-like state, but in different ways: zolpidem primarily reduces the latency to NREM sleep, and is a controlled substance taken by many people to help them sleep; DEX produces prominent slow wave activity in the electroencephalogram (EEG) resembling stage 2 NREM sleep, but with complications of hypothermia and lowered blood pressure-it is used for long term sedation in hospital intensive care units-under DEX-induced sedation patients are arousable and responsive, and this drug reduces the risk of delirium. DEX, and another α2 adrenergic agonist xylazine, are also widely used in veterinary clinics to sedate animals. Here we review how these two different classes of sedatives, zolpidem and dexmedetomideine, can selectively interact with some nodal points of the circuitry that promote wakefulness allowing the transition to NREM sleep. Zolpidem enhances GABAergic transmission onto histamine neurons in the hypothalamic tuberomammillary nucleus (TMN) to hasten the transition to NREM sleep, and DEX interacts with neurons in the preoptic hypothalamic area that induce sleep and body cooling. This knowledge may aid the design of more precise acting sedatives, and at the same time, reveal more about the natural sleep-wake circuitry.
- Evaluation of benzodiazepines and zolpidem in nails and their stability after prolonged exposure to chlorinated water. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Jan 31; 152:137-142
- The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long...
The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long-term monitoring of anxiolytic and hypnotic drugs. Both fingernail and toenail samples (1-2 mm) were collected by clipping the excess overhang of the nail from volunteers and from postmortem cases. They were washed twice with organic solvents, dried under nitrogen stream, pulverized, immersed in a methanol solution (internal standard: diazepam-D5) and sonicated up to two hours. The solution was then direct injected in the LC-MS/MS system. Mass spectrometry was set in MRM mode, selecting two transitions for each substance. 32 analytes among benzodiazepines, metabolites and hypnotics were included in the list. The method fulfilled the internationally required criteria for validation. Limits of detection ranged from 0.03 pg/mg (zolpidem) to 13.1 pg/mg (bromazepam). 9 subjects under therapy were positive at 7 different benzodiazepines and/or metabolites (lorazepam, desalkylflurazepam, bromazepam, diazepam, alprazolam, lormetazepam and prazepam), while 5 molecules were measured in 4 postmortem cases (diazepam, desmethyldiazepam, delorazepam, 7-aminoclonazepam and zolpidem). In vitro experiments on eight authentic samples suggested that benzodiazepines in nails are influenced by the prolonged exposure to chlorinated water.
- Parasomnias and Sleep-Related Movement Disorders in Older Adults. [Review]
- SMSleep Med Clin 2018; 13(1):51-61
- Parasomnias and sleep-related movement disorders are important problems in older adults. Sleep paralysis is rare, but may occur in families. In a minority of patients with disorders of arousal, the e...
Parasomnias and sleep-related movement disorders are important problems in older adults. Sleep paralysis is rare, but may occur in families. In a minority of patients with disorders of arousal, the episodes persist until the age of 70. Zolpidem and other medications may induce sleepwalking and sleep-related eating. Most patients with idiopathic rapid eye movement (REM) sleep behavior disorder eventually develop Parkinson's disease or dementia with Lewy bodies. Anti-IgLON5 disease includes abnormal behaviors in NREM and REM sleep. Restless legs syndrome prevalence increases with age. A severe form of periodic limb movements in sleep may mimic REM sleep behavior disorder.
- Effect of Sedative-Hypnotic Medicines on Mortality in Peritoneal Dialysis Patients with Sleep Disorders: A Retrospective Cohort Study. [Journal Article]
- BPBlood Purif 2017 Dec 12; 45(1-3):95-101
- CONCLUSIONS: Sedative-hypnotic medication was more often used by older patients and patients with a longer duration of CAPD. There was no association between these agents and all-cause mortality in CAPD patients with sleep disorders.
- Zolpidem efficacy and safety in disorders of consciousness. [Journal Article]
- BIBrain Inj 2018; 32(4):530-531
- Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexp...
Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.
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- Aeromedical solutions for aerospace safety. [Journal Article]
- MJMed J Armed Forces India 2017; 73(4):384-387
- All facets of activity in the speciality of Aviation Medicine are essentially aimed at enhancing aerospace safety. This paper highlights some innovative changes brought about by Aerospace Medicine in...
All facets of activity in the speciality of Aviation Medicine are essentially aimed at enhancing aerospace safety. This paper highlights some innovative changes brought about by Aerospace Medicine in the three major fields of the speciality namely, medical evaluation, aeromedical training and research. Based on lab and field studies, military aircrew are now permitted flying with Modifinil as 'Go' Pill and Zolpidem as 'No-Go' Pill during sustained operations. Several other drugs for disabilities like Hypertension and CAD are now permitted for aviators. Comprehensive revision of policy permitting early return to flying is an on-going process. OPRAM courses for all three streams of aircrew in IAF have contributed to reduce aircraft accident rates. Human Engineering Consultancy and expert advice is provided by specialists at IAM as well as those in the field. In future, the country needs to provide better post-service opportunities to aerospace medicine specialists. This, in turn, will attract bright young minds to the specialty. The ISRO Humanin-Space programme will be an exciting challenge for all in this unique field. Aerospace Medicine continues to provide aerospace safety solutions to the IAF and the aviation industry. The nation needs to continue to utilize and support this specialty.