Estazolam is prescribed for the short-term treatment of certain sleep disorders. It is an effective hypnotic drug showing efficacy in increasing the time spent asleep as well as reducing awakenings during the night. Combination with non-pharmacological options for sleep management results in long-term improvements in sleep quality after discontinuation of short-term estazolam therapy.[5][6] Estazolam is also sometimes used as a preoperative sleep aid. It was found to be superior totriazolam in side effect profile in preoperative patients in a trial.[7] Estazolam also hasanxiolytic properties and due to its long half-life can be an effective short-term treatment for insomnia associated withanxiety.[8]
A hang-over effect commonly occurs with next day impairments of mental and physical performance.[9] Other side effects of estazolam includesomnolence,dizziness,hypokinesia, and abnormalcoordination.[10]
In September 2020, the U.S.Food and Drug Administration (FDA) required theboxed 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.[11]
The main safety concern of benzodiazepines such as estazolam is abenzodiazepine dependence and the subsequentbenzodiazepine withdrawal syndrome which can occur upon discontinuation of the estazolam. A review of the literature found that long-term use of benzodiazepines such as estazolam is associated withdrug tolerance,drug dependence,rebound insomnia and CNS related adverse effects. Estazolam should only be used short term and at the lowest effective dose to avoid complications related to long-term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality.[12][13] The short-term benefits of benzodiazepines on sleep begin to reduce after a few days due totolerance to the hypnotic effects of benzodiazepines in the elderly.[14]
Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children,alcohol or drug-dependent individuals and individuals withcomorbidpsychiatric disorders.[15]
Estazolam is classed as a "triazolo" benzodiazepine drug.[16] Estazolam exerts its therapeutic effects via its benzodiazepines receptor agonist properties.[17] Estazolam at high doses decreases histamine turnover via its action at the benzodiazepine-GABA receptor complex in mouse brains.[18]
Peak plasma levels are achieved within 1–6 hours. Estazolam is an intermediate actingbenzodiazepine. Theelimination half life of estazolam is an average of 19 hours, with a range of 8–31 hours.[19][20] The major metabolite of estazolam is 4-hydroxyestazolam.[21] Other identified metabolites include 1-oxo-estazolam, 4'-hydroxy-estazolam, andbenzophenone.[2]
Alcohol enhances thesedativehypnotic properties of estazolam.[22] In package inserts, the manufacturer clearly warns about an interaction withritonavir, and although clinical interactions of ritonavir with estazolam have not yet been described, the lack of clinical descriptions of the interactions does not negate the seriousness of the interaction.[23]
An animal study in rabbits demonstrated that estazolam induces a drowsy pattern of spontaneousEEG including high voltage slow waves and spindle bursts increase in thecortex andamygdala, while thehippocampal theta rhythm is desynchronized. Also low voltage fast waves occur particularly in thecortical EEG. The EEG arousal response toauditory stimulation and to electric stimulation of the mesencephalic reticular formation,posteriorhypothalamus and centromedianthalamus is significantly suppressed. Thephotic driving response elicited by a flash light in thevisual cortex is significantly suppressed by estazolam.[24]
A primate study found that estazolam has abuse potential.[25] Two types of drug misuse can occur; recreational misuse, where the drug is taken to achieve a high or when the drug is continued long term against medical advice.[26] Estazolam became notorious in 1998 when a large amount of an 'herbal sleeping mix' called Sleeping Buddha was recalled from the shelves after the FDA discovered that it contained estazolam.[27] In 2007, a Canadian product called Sleepees was recalled after it was found to contain undeclared estazolam.[28][29]
^Roehrs T, Zorick F, Lord N, Koshorek GL, Roth T (June 1983). "Dose-related effects of estazolam on sleep of patients with insomnia".Journal of Clinical Psychopharmacology.3 (3):152–156.doi:10.1097/00004714-198306000-00002.PMID6135720.S2CID9143614.
^Mauro C, Sperlongano P (September 1987). "[Controlled clinical evaluation of 2 hypnotic triazole benzodiazepines, estazolam and triazolam, used the night before surgical interventions]".Minerva Medica (in Italian).78 (18):1381–1384.PMID2889169.
^Post GL, Patrick RO, Crowder JE, Houston J, Ferguson JM, Bielski RJ, et al. (August 1991). "Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study".Journal of Clinical Psychopharmacology.11 (4):249–253.doi:10.1097/00004714-199108000-00005.PMID1918423.S2CID7890993.
^Müller KW, Müller-Limmroth W, Strasser H (1982). "[Alterations of sleep stage pattern in human beings and hang-over effects under the influence of estazolam/2nd Comm.: Studies on the hang-over effect in psycho-physiological performance (author's transl)]".Arzneimittel-Forschung (in German).32 (4):456–460.PMID6125155.
^Pierce MW, Shu VS, Groves LJ (March 1990). "Safety of estazolam. The United States clinical experience".The American Journal of Medicine.88 (3A):12S –17S.doi:10.1016/0002-9343(90)90280-Q.PMID1968713.
^Grad RM (November 1995). "Benzodiazepines for insomnia in community-dwelling elderly: a review of benefit and risk".The Journal of Family Practice.41 (5):473–481.PMID7595266.
^Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, et al. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome".Annales Pharmaceutiques Françaises.67 (6):408–413.doi:10.1016/j.pharma.2009.07.001.PMID19900604.
^Braestrup C, Squires RF (April 1978). "Pharmacological characterization of benzodiazepine receptors in the brain".European Journal of Pharmacology.48 (3):263–270.doi:10.1016/0014-2999(78)90085-7.PMID639854.
^Akbarzadeh T, Tabatabai SA, Khoshnoud MJ, Shafaghi B, Shafiee A (March 2003). "Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists".Bioorganic & Medicinal Chemistry.11 (5):769–773.doi:10.1016/S0968-0896(02)00469-8.PMID12538007.
^Oishi R, Nishibori M, Itoh Y, Saeki K (May 1986). "Diazepam-induced decrease in histamine turnover in mouse brain".European Journal of Pharmacology.124 (3):337–342.doi:10.1016/0014-2999(86)90236-0.PMID3089825.
^Allen MD, Greenblatt DJ, Arnold JD (1979). "Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine".Psychopharmacology.66 (3):267–274.doi:10.1007/BF00428318.PMID43552.S2CID23882114.
^Mancinelli A, Guiso G, Garattini S, Urso R, Caccia S (March 1985). "Kinetic and pharmacological studies on estazolam in mice and man".Xenobiotica; the Fate of Foreign Compounds in Biological Systems.15 (3):257–265.doi:10.3109/00498258509045357.PMID2862746.
^Miura M, Otani K, Ohkubo T (May 2005). "Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam".Xenobiotica; the Fate of Foreign Compounds in Biological Systems.35 (5):455–465.doi:10.1080/00498250500111612.PMID16012077.S2CID10576075.
^Johanson CE (March 1987). "Benzodiazepine self-administration in rhesus monkeys: estazolam, flurazepam and lorazepam".Pharmacology, Biochemistry, and Behavior.26 (3):521–526.doi:10.1016/0091-3057(87)90159-6.PMID2883668.S2CID21917850.
^Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds".The Journal of Clinical Psychiatry.66 (Suppl 9):31–41.PMID16336040.
.jpg)
This article incorporates text from this source, which is in thepublic domain.
