Quazepam, sold under the brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s.[2] Quazepam is used for the treatment of insomnia, including sleep induction and sleep maintenance.[3] Quazepam induces impairment of motor function and has relatively (and uniquely) selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines (due to its novel receptor-subtype selectivity).[4][5] Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.[6]
It was patented in 1970 and came into medical use in 1985.[7]
Medical uses
Quazepam is used for short-term treatment of insomnia related to sleep induction or sleep maintenance problems and has demonstrated superiority over other benzodiazepines, such as temazepam. It had a lower incidence of side effects than temazepam, including less sedation, amnesia, and motor impairment.[8][9][10][11] Usual dosage is 7.5 to 15 mg orally at bedtime.[12]
Quazepam has fewer side effects than other benzodiazepines and less potential to induce tolerance and rebound effects.[14][15] There is significantly less potential for quazepam to induce respiratory depression or to adversely affect motor coordination than other benzodiazepines.[16] The different side effect profile of quazepam may be due to its more selective binding profile to type 1 benzodiazepine receptors.[17][18]
In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[23]
Tolerance and dependence
Tolerance may occur to quazepam, but more slowly than seen with other benzodiazepines such as triazolam.[24] Quazepam causes significantly less drug tolerance and withdrawal symptoms including less rebound insomnia upon discontinuation compared to other benzodiazepines.[25][26][27][28] Quazepam may cause less rebound effects than other type1 benzodiazepine receptor selective nonbenzodiazepine drugs due to its longer half-life.[29] Short-acting hypnotics often cause next-day rebound anxiety. Quazepam, due to its pharmacological profile, does not cause next-day rebound withdrawal effects during treatment.[30]
No firm conclusions can be drawn, however, about whether long-term use of quazepam does not produce tolerance, as few, if any, long-term clinical trials extending beyond 4 weeks of chronic use have been conducted.[31] Quazepam should be withdrawn gradually if used beyond 4 weeks of use to avoid the risk of a severe benzodiazepine withdrawal syndrome developing. Very high dosage administration over prolonged periods of time, up to 52 weeks, of quazepam in animal studies provoked severe withdrawal symptoms upon abrupt discontinuation, including excitability, hyperactivity, convulsions, and the death of two of the monkeys due to withdrawal-related convulsions. More monkeys died however, in the diazepam-treated monkeys.[32] In addition, it has now been documented in the medical literature that one of the major metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), which is long-acting and prone to accumulation, binds unselectively to benzodiazepine receptors, thus quazepam may not differ all that much pharmacologically from other benzodiazepines.[33]
Special precautions
Benzodiazepines require special precaution if used during pregnancy, in children, alcohol, or drug-dependent individuals, and individuals with comorbidpsychiatric disorders.[34]
Quazepam is more tolerable for elderly patients compared to flurazepam due to its reduced next-day impairments.[37] However, another study showed marked next-day impairments after repeated administration due to the accumulation of quazepam and its long-acting metabolites. Thus, the medical literature shows conflicts on quazepam's side effect profile.[38] A further study showed significant balance impairments combined with an unstable posture after administration of quazepam in test subjects.[39]
An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines, including quazepam, the nonbenzodiazepinesedative/hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative/hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly people with chronic insomnia.[40]
Interactions
The absorption rate is likely to be significantly reduced if quazepam is taken in a fasted state, reducing the hypnotic effect of quazepam. If 3 or more hours have passed since eating food, then some food should be eaten before taking quazepam.[41][42]
Pharmacology
Quazepam is a trifluoroalkyl type of benzodiazepine. Quazepam is unique amongst benzodiazepines in that it selectively targets the GABAA α1 subunit receptors, which are responsible for inducing sleep. Its mechanism of action is very similar to zolpidem and zaleplon in its pharmacology and can successfully substitute for zolpidem and zaleplon in animal studies.[43][44][45]
Quazepam is selective for type I benzodiazepine receptors containing the α1 subunit, similar to other drugs such as zaleplon and zolpidem. As a result, quazepam has little or no muscle-relaxant properties. Most other benzodiazepines are unselective and bind to type1 GABAA receptors and type2 GABAA receptors. Type1 GABAA receptors include the α1 subunit containing GABAA receptors, which are responsible for the hypnotic properties of the drug. Type 2 receptors include the α2, α3 and α5 subunits, which are responsible for anxiolytic action, amnesia, and muscle relaxant properties.[46][47] Thus, quazepam may have less side effects than other benzodiazepines, but, it has a very long half-life of 25 hours, which reduces its benefits as a hypnotic due to likely next day sedation. It also has two active metabolites with half-lives of 28 and 79 hours. Quazepam may also cause less drug tolerance than other benzodiazepines such as temazepam and triazolam, perhaps due to its subtype selectivity.[48][49][50][51] The longer half-life of quazepam may have the advantage, however, of causing less rebound insomnia than shorter-acting subtype selective nonbenzodiazepines.[9][29] However, one of the major metabolites of quazepam, the N-desmethyl-2-oxoquazepam (aka N-desalkylflurazepam), binds unselectively to both type1 and type2 GABAA receptors. The N-desmethyl-2-oxoquazepam metabolite also has a very long half-life and likely contributes to the pharmacological effects of quazepam.[52]
Pharmacokinetics
Quazepam has an absorption half-life of 0.4 hours with a peak in plasma levels after 1.75 hours. It is eliminated both renally and through feces.[53] The active metabolites of quazepam are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. The N-desalkyl-2-oxoquazepam metabolite has only limited pharmacological activity compared to the parent compound quazepam and the active metabolite 2-oxoquazepam. [citation needed] Quazepam and its major active metabolite 2-oxoquazepam both show high selectivity for the type1 GABAA receptors.[54][55][56][57] The elimination half-life range of quazepam is between 27 and 41 hours.[31]
Mechanism of action
Quazepam modulates specific GABAA receptors via the benzodiazepine site on the GABAA receptor. This modulation enhances the actions of GABA, causing an increase in the opening frequency of the chloride ion channel, which results in an increased influx of chloride ions into the GABAA receptors. Quazepam, unique amongst benzodiazepine drugs, selectively targets type 1 benzodiazepine receptors, which results in reduced sleep latency and promotion of sleep.[58][59][60] Quazepam also has some anticonvulsant properties.[61]
EEG and sleep
Quazepam has potent sleep-inducing and sleep-maintaining properties.[62][63] Studies in both animals and humans have demonstrated that EEG changes induced by quazepam resemble normal sleep patterns, whereas other benzodiazepines disrupt normal sleep. Quazepam promotes slow-wave sleep.[64][65] This positive effect of quazepam on sleep architecture may be due to its high selectivity for type 1 benzodiazepine receptors, as demonstrated in animal and human studies. This makes quazepam unique in the benzodiazepine family of drugs.[66][67]
Quazepam is a drug with the potential for misuse. Two types of drug misuse can occur: either recreational misuse, where the drug is taken to achieve a high, or when the drug is continued long term against medical advice.[68]
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Si ce bandeau n'est plus pertinent, retirez-le. Cliquez ici pour en savoir plus. Cet article ne cite pas suffisamment ses sources (octobre 2018). Si vous disposez d'ouvrages ou d'articles de référence ou si vous connaissez des sites web de qualité traitant du thème abordé ici, merci de compléter l'article en donnant les références utiles à sa vérifiabilité et en les liant à la section « Notes et références ». En pratique : Quelles sources sont attendues ? Comm…
Questa voce sull'argomento stagioni delle società calcistiche italiane è solo un abbozzo. Contribuisci a migliorarla secondo le convenzioni di Wikipedia. Segui i suggerimenti del progetto di riferimento. Voce principale: Associazione Sportiva Dilettantistica Sangiovannese 1927. Associazione Calcio SangiovanneseStagione 2008-2009Sport calcio Squadra Sangiovannese Allenatore Fabrizio Tazzioli poi Fabio Fraschetti Presidente Andrea Failli Seconda Divisione12º posto nel girone B. Maggio…
Le informazioni riportate non sono consigli medici e potrebbero non essere accurate. I contenuti hanno solo fine illustrativo e non sostituiscono il parere medico: leggi le avvertenze. Questa voce o sezione sugli argomenti disturbi psichici e malattie non cita le fonti necessarie o quelle presenti sono insufficienti. Puoi migliorare questa voce aggiungendo citazioni da fonti attendibili secondo le linee guida sull'uso delle fonti. Segui i suggerimenti del progetto di riferimento. Disturbo d…
Kbk wz. 2005 Jantar The wz. 2005 Jantar Jenis Bullpup Senapan serbu Negara asal Polandia Sejarah produksi Perancang WAT Tahun 2005 Produsen Łucznik Arms Factory Jumlah produksi 1 Spesifikasi Berat 3,8 kg (Jantar-M) Panjang 743 mm Panjang laras 457 mm Kaliber 5,56 x 45 mm NATO Mekanisme Operasi gas, rotating bolt Kecepatan peluru 920 m/s Amunisi Kotak magazen isi 30 butir Kbk wz. 2005 Jantar adalah senapan serbu bullpup asal Polandia hasil desain Wojskowa Akademia Techn…
The military ranks of Lebanon are the military insignia used by the Lebanese Armed Forces. Being a former French mandate, Lebanon shares a rank structure similar to that of France.[1] Commissioned officer ranks The rank insignia of commissioned officers. Rank group General / flag officers Senior officers Junior officers Officer cadet Lebanese Ground Forces[2]vte عمادEimad لواءLiwa عميدAmid عقيدAqid مقدمMuqaddam رائدRa'id نقيبNaqib ملازم أو…
American actress (born 1990) Stephanie HsuHsu at the 2023 Santa Barbara International Film FestivalBornStephanie Ann Hsu (1990-11-25) November 25, 1990 (age 33)Torrance, California, U.S.Alma materNew York University Tisch School of the ArtsOccupationActressYears active2010–presentChinese nameTraditional Chinese許瑋倫TranscriptionsStandard MandarinHanyu PinyinXǔ WěilúnWade–GilesHsu Wei-lunIPA[ɕù wèɪ.lwə̌n] Stephanie Ann Hsu (/ˈʃuː/ SHOO; b…
Pour des articles plus généraux, voir Chronologie des États-Unis et 1990. Éphémérides Chronologie des États-Unis 1987 1988 1989 1990 1991 1992 1993Décennies aux États-Unis :1960 1970 1980 1990 2000 2010 2020 Chronologie dans le monde 1987 1988 1989 1990 1991 1992 1993Décennies :1960 1970 1980 1990 2000 2010 2020Siècles :XVIIIe XIXe XXe XXIe XXIIeMillénaires :-Ier Ier IIe IIIe Chronologies géo…
1966 studio album by The DeepPsychedelic MoodsStudio album by The DeepReleasedOctober 1966RecordedAugust 19–20, 1966StudioCameo-Parkway Studios, Philadelphia, PAGenre Psychedelic rock garage rock Length29:43LabelCameo-ParkwayProducerThe Deep, Mark BarkanThe Deep chronology Psychedelic Moods(1966) Psychedelic Psoul(1967) Psychedelic Moods is the debut album by the American psychedelic rock band, The Deep, and was released on Cameo-Parkway Records in October 1966 (see 1966 in music). The…
Lilia Osterloh Nazionalità Stati Uniti Altezza 170 cm Peso 60 kg Tennis Termine carriera 2011 Carriera Singolare1 Vittorie/sconfitte 385 - 366 Titoli vinti 0 Miglior ranking 41º (23 aprile 2001) Risultati nei tornei del Grande Slam Australian Open 1T (1999, 2000, 2001, 2002, 2008) Roland Garros 2T (1999) Wimbledon 4T (2000) US Open 4T (2000) Doppio1 Vittorie/sconfitte 192 – 215 Titoli vinti 3 Miglior ranking 77º (23 agosto 1999) Risultati nei tornei del Grande …
Questa voce o sezione contiene informazioni riguardanti un film in produzione, atteso o annunciato. Il contenuto potrebbe cambiare radicalmente non appena maggiori informazioni saranno disponibili. Per favore, non aggiungere speculazioni alla voce. Inside Out 2Da sinistra a destra: Imbarazzo, Ansia, Invidia e Noia in una scena del filmLingua originaleinglese Paese di produzioneStati Uniti d'America Anno2024 Genereanimazione, commedia, fantastico RegiaKelsey Mann SceneggiaturaMeg LeFauve …