China
Africa
Explore chapters and articles related to this topic
Parasomnias
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Because adults often have vigorous or frankly violent episodes, efforts toward immediate control should precede or be concurrent with psychotherapeutic measures, even in cases with a clearly psychogenic cause. Clonazepam (O.S to 2.0 mg) or carbamazepine (100 to 200 mg) 2 hours before bedtime is most often used, although phenytoin (100 to 200 mg) or other benzodiazepines including flurazepam (IS to 30 mg) and lorazepam (O.S to 2.0 mg) may also be useful. Combining a benzodiazepine with carbamazepine or phenytoin is sometimes necessary to achieve satisfactory results. Usually events can be entirely suppressed or, at least, adequately controlled with drug dosages below those used for daytime seizure control. Possibly patients in whom psychological factors are thought to be most important respond least well to medication, although even in those patients control of episodes with medication can be effected.
Pharmacokinetic determinants of clinical activity
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
Elimination half-lives are also critical parameters for hypnotic benzodiazepines. Brain levels of these agents need to be sufficiently high during the night to provide effective sleep induction and maintenance, but to be low, or absent, during the day to avoid daytime sedation (Figure 7.4). The first generation of hypnotic benzodiazepines, such as flurazepam and nitrazepam, were supplanted by shorter-acting drugs largely because of the next-day sedation seen with the former due to persistence of active drug in the brain. These unwanted residual effects are particularly troublesome for active individuals who need to be alert and reactive in the workplace during the day. The most widely used hypnotic benzodiazepines today have elimination half-lives of 8 hours or less (Table 7.2).
Adherence and the Elderly
Published in Lynn B. Myers, Kenny Midence, Adherence to Treatment in Medical Conditions, 2020
James C. McElnay, C. Rosaleen McCallion
The model described above indicated that elderly patients who took diuretics were almost three times more likely to report good adherence compared to elderly patients who did not take diuretics. These results add weight to the findings of the SHEP (Systolic Hypertension in the Elderly Program) pilot study which provided evidence, based on two objective measures of adherence, namely pill-counts and urine tests, as well as self-reported data, that high levels of adherence occur with antihypertensive treatments among the elderly (Black et al., 1987). On the other hand, patients who were prescribed bronchodilators were shown to be 2.4 times more likely to report non-adherence than patients who did not. These findings are in agreement with the results of others (Rand and Wise, 1994; Horn et al., 1990; Tettersell, 1993). Adverse effects of benzodiazepines in the elderly have been documented frequently in the literature, for example, studies have shown that elderly people are more sensitive to the sedative effects of diazepam after short-term administration than younger adults (Montamat et al., 1989). The benzodiazepines, particularly those with longer half-lives, have been implicated as one of the drug classes associated with falls leading to hip fracture in elderly patients (Gales and Menard, 1995; Cummings et al., 1995). Excessive drowsiness, confusion and ataxia, are the most commonly reported adverse drug reactions to the longer acting benzodiazepines such as flurazepam (Gurwitz and Avorn, 1991). Such adverse effects are likely to decrease adherence to medication regimens.
Do Placebos Primarily Affect Subjective as Opposed to Objective Measures? A Meta-Analysis of Placebo Responses in Insomnia RCTs
Published in Behavioral Sleep Medicine, 2023
Alexandria Muench, Joshua Giller, Knashawn H. Morales, Elizabeth Culnan, Waliuddin Khader, Ted J. Kaptchuk, William V. McCall, Michael L. Perlis
The keywords utilized included insomnia, treatment, randomized controlled trial (RCT), clinical trial, medication class, and medication name (i.e., BZRAs: flurazepam, quazepam, estazolam, temazepam, triazolam, clonazepam, lorazepam, alprazolam, diazepam, chlordiazepoxide, zolpidem, zaleplon, and eszopiclone; DORAs: suvorexant, almorexant, and lemborexant; MELAs: ramelteon; SADs: amitriptyline, doxepin, trazodone, and mirtazapine). The queries elicited 329 articles, where 17 met inclusion criteria. Please note that the reason multiple queries were conducted was because many of the drug classes include a variety of medications and it was our preference to identify RCTs by each specific medication. For example, “Clinical Trial” + “Insomnia” + “Flurazepam” vs. “Clinical Trial” + “Insomnia” + “Temazepam,” etc.
The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis
Published in International Journal of Neuroscience, 2019
Barbara Sinner, Julia Steiner, Manuela Malsy, Bernhard M. Graf, Anika Bundscherer
We observed an increase in alpha 1 mRNA subunit expression of the GABAA immediately following washout of 100 nM midazolam for both time periods. This was associated with a decrease in BAX/Bcl-2 ratio and did not affect Caspase-3 expression. This might indicate that in case of down-regulated glutamate-receptors the up-regulation of GABAA receptor seems to be neuroprotective. Chronic administration of GABAA receptor agonists alters the qualitative and quantitative expression of GABA receptor mRNA and peptides [20,21]. The chronic exposure to GABA decreases the alpha 1 subunit mRNA in embryonic chick neurons and decreases the level of mRNA and peptides for the alpha 2 and alpha 3 subunits in mammalian primary cultured cortical neurons [21,22]. The chronic exposure of rat hippocampal or cortical neurons to the benzodiazepine flurazepam results in a decreased alpha 1, gamma 2 and alpha 5 subunit mRNA [22,23]. Ethanol, another drug activating GABAA receptors alters alpha 1 mRNA and peptide levels and increases alpha 4 expression in the cerebral cortex model [20,24,25]. However, these data result from chronic blockade experiments in mature brains.
Evaluating lemborexant for the treatment of insomnia
Published in Expert Opinion on Pharmacotherapy, 2021
Benzodiazepines act by binding to a site on the GABA-A receptor and increasing the effect of the neurotransmitter GABA when it binds to this receptor [21]. This decreases neural activity and can have broad effects on central nervous system function including myorelaxation, anxiolysis, anticonvulsant effects, and sedation. Although many benzodiazepines are available and have shown efficacy in clinical trials, particularly for improving sleep duration [4,21], they are generally only indicated for short-term treatment [22,23] because of a paucity of data on long-term treatment. However, they are relatively contraindicated with opioids [22,23] and data are lacking on the risk–benefit ratio of longer term use. Additionally, there is a risk of dependence and withdrawal symptoms associated with these medications, particularly with higher doses, longer duration, older age, alcohol dependence, and use of the high-potency, short-acting options [24]. Adverse events associated with benzodiazepines can include daytime sedation, cognitive impairment, and motor impairment [25]. Although many benzodiazepines have been approved by the United States Food and Drug Administration (FDA) for treatment of insomnia (the short-acting temazepam, triazolam, and estazolam, and the longer-acting flurazepam and quazepam), the AASM clinical practice guidelines recommend only temazepam for treatment of both sleep onset and sleep maintenance insomnia, and triazolam for sleep onset insomnia [19] because they are short-acting and therefore have a lower likelihood of next day residual effects [26]. In the current United States market, the benzodiazepines are not among the agents most commonly prescribed for insomnia [27].