- Medicines associated with dependence or withdrawal: a mixed-methods public health review and national database study in England. [Journal Article]Lancet Psychiatry 2019LP
- CONCLUSIONS: In 1 year over a quarter of the adult population in England had a prescription dispensed for antidepressants, opioids (for non-cancer pain), gabapentinoids, benzodiazepines, or Z-drugs. Long-term (>12 months) prescribing is common, despite being either not recommended by clinical guidelines or of doubtful efficacy in many cases. Enhanced national and local monitoring, better guidance for personalised care, and better doctor-patient decision making are needed.
- Use of short-acting and long-acting hypnotics and the risk of fracture: a critical analysis of associations in a nationwide cohort. [Journal Article]Osteoporos Int 2019OI
- CONCLUSIONS: The use of short-acting and long-acting hypnotics is associated with an increased risk of fracture. This risk was highest before initiation of treatment and remained after end of therapy. The results suggest that the increased risk during treatment is influenced by other factors such as underlying disease.
- Reintroduction of quazepam: an update on comparative hypnotic and adverse effects. [Journal Article]Int Clin Psychopharmacol 2019; 34(6):275-285IC
- Insomnia is a prevalent disorder that affects over one-third of the U.S. population to varying degrees and is highly disruptive towards quality of life. Pharmacological treatments for insomnia include benzodiazepines (BZs) and the non-BZ 'Z-drugs' (zolpidem, zaleplon, eszopiclone, zopiclone), which are amongst the most widely prescribed medications. Yet, these agents can produce adverse effects s…
Insomnia is a prevalent disorder that affects over one-third of the U.S. population to varying degrees and is highly disruptive towards quality of life. Pharmacological treatments for insomnia include benzodiazepines (BZs) and the non-BZ 'Z-drugs' (zolpidem, zaleplon, eszopiclone, zopiclone), which are amongst the most widely prescribed medications. Yet, these agents can produce adverse effects such as tolerance to the hypnotic effect, rebound insomnia, next-day residual drowsiness, as well as amnesia and complex behaviours such as sleep-walking, sleep-eating and sleep-driving. Quazepam, one of the five BZ approved for treatment of insomnia, was recently relaunched to the U.S. market in 2016 and is distinguished amongst hypnotic BZ by unique pharmacological characteristics including selectivity for sleep-promoting α1-subunit containing γ-aminobutyric acid (GABA-A) receptors and a significantly lower relative receptor binding affinity. These features likely drive the decreased rate of adverse events seen clinically with quazepam, such as tolerance, rebound insomnia and amnesic behaviours, compared with other BZ. Given the recent reintroduction of quazepam as a pharmacotherapeutic option, and the lack of head-to-head comparative trials against newer agents, the purpose of this review is to provide an update on distinguishing features of quazepam with regard to its pharmacology, pharmacokinetics, sleep efficacy and potential adverse effects compared to other agents used for insomnia.
- Evaluation of the prescribing practices of nonbenzodiazepine, benzodiazepine receptor agonist hypnotics in adults at a federally qualified health center. [Journal Article]J Am Pharm Assoc (2003) 2019 Jul - Aug; 59(4S):S146-S150JA
- CONCLUSIONS: Prescribing rates of zolpidem in 10-mg doses to female patients were high, indicating that providers could benefit from further education on this topic. In the population, and in adults age 65 years and older, Z-drug prescribing in an FQHC was low compared with available prescribing rates.
- Drug Interactions in Space: a Cause for Concern? [Journal Article]Pharm Res 2019; 36(8):114PR
- CONCLUSIONS: Most potential DDIs likely to be encountered in space are unestablished even in terrestrial medicine and their assignment is based on class-effects. Yet, some drug combinations may be associated with clinically-relevant consequences. Future DDI rating should be adjusted to space-related outcomes. Until that happens, it would be advisable to avoid non-established drug combinations in space when possible.
- Case-control study examining the association between hip fracture and zaleplon use in older adults. [Letter]Postgrad Med J 2019; 95(1122):233-234PM
- Time Course of Aldehyde Oxidase and Why It Is Nonlinear. [Journal Article]Drug Metab Dispos 2019; 47(5):473-483DM
- Many promising drug candidates metabolized by aldehyde oxidase (AOX) fail during clinical trial owing to underestimation of their clearance. AOX is species-specific, which makes traditional allometric studies a poor choice for estimating human clearance. Other studies have suggested using half-life calculated by measuring substrate depletion to measure clearance. In this study, we proposed using …
Many promising drug candidates metabolized by aldehyde oxidase (AOX) fail during clinical trial owing to underestimation of their clearance. AOX is species-specific, which makes traditional allometric studies a poor choice for estimating human clearance. Other studies have suggested using half-life calculated by measuring substrate depletion to measure clearance. In this study, we proposed using numerical fitting to enzymatic pathways other than Michaelis-Menten (MM) to avoid missing the initial high turnover rate of product formation. Here, product formation over a 240-minute time course of six AOX substrates-O6-benzylguanine, N-(2-dimethylamino)ethyl)acridine-4-carboxamide, zaleplon, phthalazine, BIBX1382 [N8-(3-Chloro-4-fluorophenyl)-N2-(1-methyl-4-piperidinyl)-pyrimido[5,4-d]pyrimidine-2,8-diamine dihydrochloride], and zoniporide-have been provided to illustrate enzyme deactivation over time to help better understand why MM kinetics sometimes leads to underestimation of rate constants. Based on the data provided in this article, the total velocity for substrates becomes slower than the initial velocity by 3.1-, 6.5-, 2.9-, 32.2-, 2.7-, and 0.2-fold, respectively, in human expressed purified enzyme, whereas the K m remains constant. Also, our studies on the role of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, show that ROS did not significantly alter the change in enzyme activity over time. Providing a new electron acceptor, 5-nitroquinoline, did, however, alter the change in rate over time for mumerous compounds. The data also illustrate the difficulties in using substrate disappearance to estimate intrinsic clearance.
- The effect of nonbenzodiazepines sedative hypnotics on apnea-hypopnea index: A meta-analysis. [Journal Article]Ann Thorac Med 2019 Jan-Mar; 14(1):49-55AT
- CONCLUSIONS: The majority of patients using NBSH did not develop any worsening of existing AHI, when using NBSH, regardless of their baseline AHI values (mild, moderate, severe, or no OSA). On average, the AHI improved minimally with NBSH and eszopiclone showed the largest difference in AHI with an MD of -5.73 events/h.
- An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions. [Journal Article]Int J Neuropsychopharmacol 2019; 22(4):270-277IJ
- CONCLUSIONS: Current data may only represent a gross underestimate of the real prevalence of Z-drug misuse. Caution should be exercised when prescribing those molecules, especially for patients with psychiatric illnesses and/or history of drug abuse. We recommend the need to invest in proactive pharmacovigilance activities to better and promptly detect, understand, and prevent any possible misuse potential of prescribed medications.
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- The impact of opiate substitution treatment on mortality risk in drug addicts: a natural experiment study [BOOK]NIHR Journals Library: Southampton (UK)BOOK
- CONCLUSIONS: Using buprenorphine as an alternative to methadone may not reduce mortality overall despite resulting in lower IRRs from shorter treatment duration. Clinical guidance needs to consider strengthening warnings about the co-prescription of a range of drugs for OST patients.