Oxazepam

Source: Wikipedia, the free encyclopedia.
Oxazepam
Clinical data
Trade namesAlepam, Generics
Addiction
liability		Low–moderate
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability92.8%
MetabolismHepatic (glucuronidation)
Elimination half-life6–9 h[3][4][5]
ExcretionRenal
Identifiers
  • 7-Chloro-3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one[6]
JSmol)
Melting point205 to 206 °C (401 to 403 °F)
  • O=C1Nc2ccc(Cl)cc2C(c2ccccc2)=NC1O
  • InChI=1S/C15H11ClN2O2/c16-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)18-15(20)14(19)17-12/h1-8,15,18,20H ☒N
  • Key:IMAUTQQURLXUGJ-UHFFFAOYSA-N ☒N
  (verify)

Oxazepam is a short-to-intermediate-acting benzodiazepine.[7][8] Oxazepam is used for the treatment of anxiety[9][10] and insomnia and in the control of symptoms of alcohol withdrawal syndrome.

It is a metabolite of

skeletal muscle relaxant properties compared to other benzodiazepines.[12]

It was patented in 1962 and approved for medical use in 1964.[13]

Medical uses

It is an intermediate-acting benzodiazepine with a slow onset of action,

off-label to treat social phobia, post-traumatic stress disorder, insomnia, premenstrual syndrome, and other conditions.[15]

Side effects

The side effects of oxazepam are similar to those of other benzodiazepines, and may include dizziness, drowsiness, headache, memory impairment, paradoxical excitement, and anterograde amnesia, but does not affect transient global amnesia.[citation needed] Side effects due to rapid decrease in dose or abrupt withdrawal from oxazepam may include abdominal and muscle cramps, convulsions, depression, inability to fall asleep or stay asleep, sweating, tremors, or vomiting.[16]

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.[17]

Tolerance, dependence and withdrawal

Oxazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence, addiction, and benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur, though, at standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen.[18]

Contraindications

Oxazepam is contraindicated in

hepatic disease
.

Special precautions

Benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, and individuals with

floppy infant syndrome.[20]

Pregnancy

Oxazepam when taken during the

metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.[21]

Interactions

As oxazepam is an active metabolite of diazepam, an overlap in possible interactions is likely with other drugs or food, with exception of the pharmacokinetic

respiratory depression, coma, and collapse. There is a risk of blood circulation collapse,[medical citation needed] possibly the same condition as blood circulation syncope, when oxazepam is used in combination with quetiapine, an antipsychotic
.

Overdose

Main article: Benzodiazepine overdose

Oxazepam is generally less toxic in overdose than other benzodiazepines.

CNS depressants such as opiates or alcohol has occurred. Symptoms of an oxazepam overdose include:[23][24][25]

Pharmacology

Main article: Benzodiazepine § Pharmacology

Oxazepam is an intermediate-acting benzodiazepine of the 3-hydroxy family; it acts on

GABA to the GABAA receptor which results in inhibitory effects on the central nervous system.[26][27] The half-life of oxazepam is between 6 and 9 hours.[5][4][28] It has been shown to suppress cortisol levels.[29] Oxazepam is the most slowly absorbed and has the slowest onset of action of all the common benzodiazepines according to one British study.[30]

Oxazepam is an active metabolite formed during the breakdown of diazepam, nordazepam, and certain similar drugs. It may be safer than many other benzodiazepines in patients with impaired liver function because it does not require hepatic oxidation, but rather, it is simply metabolized by glucuronidation, so oxazepam is less likely to accumulate and cause adverse reactions in the elderly or people with liver disease. Oxazepam is similar to lorazepam in this respect.[31] Preferential storage of oxazepam occurs in some organs, including the heart of the neonate. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate, and withdrawal of oxazepam during pregnancy and breast feeding is recommended, as oxazepam is excreted in breast milk.[32]

2 mg of oxazepam equates to 1 mg of diazepam according to the benzodiazepine equivalency converter, therefore 20 mg of oxazepam according to BZD equivalency equates to 10 mg of diazepam and 15 mg oxazepam to 7.5 mg diazepam (rounded up to 8 mg of diazepam).[33] Some BZD equivalency converters use 3 to 1 (oxazepam to diazepam), 1 to 3 (diazepam to oxazepam) as the ratio (3:1 and 1:3), so 15 mg of oxazepam would equate to 5 mg of diazepam.[34]

Chemistry

Oxazepam exists as a

epimerization that occur at different pH levels, it was determined that there would be no therapeutic benefit to the administration of a single enantiomer over the racemic mixture.[36]

Frequency of use

Oxazepam, along with diazepam, nitrazepam, and temazepam, were the four benzodiazepines listed on the pharmaceutical benefits scheme and represented 82% of the benzodiazepine prescriptions in Australia in 1990–1991.[37] It is in several countries the benzodiazepine of choice for novice users, due to a low chance of accumulation and a relatively slow absorption speed.[38]

Society and culture

Misuse

See also:
Benzodiazepine drug misuse

Oxazepam has the potential for misuse, defined as taking the drug to achieve a high, or continuing to take the drug in the long term against medical advice.[39] Benzodiazepines, including diazepam, oxazepam, nitrazepam, and flunitrazepam, accounted for the largest volume of forged drug prescriptions in Sweden from 1982 to 1986. During this time, a total of 52% of drug forgeries were for benzodiazepines, suggesting they were a major prescription drug class of abuse.[40]

However, due to its slow rate of absorption and its slow onset of action,[30] oxazepam has a relatively low potential for abuse compared to some other benzodiazepines, such as temazepam, flunitrazepam, or triazolam. This is similar to the varied potential for abuse between different drugs of the barbiturate class.[41]

Legal status

Oxazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[42]

Brand names

It is marketed under many brand names worldwide, including: Alepam, Alepan, Anoxa, Anxiolit, Comedormir, durazepam, Murelax, Nozepam, Oksazepam, Opamox, Ox-Pam, Oxa-CT, Oxabenz, Oxamin, Oxapam, Oxapax, Oxascand, Oxaze, Oxazepam, Oxazépam, Oxazin, Oxepam, Praxiten, Purata, Selars, Serax, Serepax, Seresta, Séresta, Serpax, Sobril, Tazepam, Vaben, and Youfei.[43]

It is also marketed in combination with

hyoscine as Novalona and in combination with alanine as Pausafrent T.[43]

Environmental concerns

In 2013, a laboratory study which exposed

predated on.[46]

On the other hand, a 2018 study from the same authors, which kept 480 European perch and 12 northern pikes in 12 ponds over 70 days, half of them control and half spiked with oxazepam, found no significant difference in either perch growth or mortality. However, it suggested that the latter could be explained by the exposed perch and pike being equally hampered by oxazepam, rather than the lack of an overall effect.[47] Lastly, a 2021 study built on these results by comparing two whole lakes filled with perch and pikes - one control while the other was exposed to oxazepam 11 days into experiment, at concentrations between 11 and 24 μg/L, which is 200 times greater than the reported concentrations in the European rivers. Even so, there were no measurable effects on pike behaviour after the addition of oxazepam, while the effects on perch behaviour were found to be negligible. The authors concluded that the effects previously attributed to oxazepam were instead likely caused by a combination of fish being stressed by human handling and small aquaria, followed by being exposed to a novel environment.[48]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ Encadré 1. Anxiolytiques à demi-vie courte (< 20 heures) et sans métabolite actif par ordre alphabétique de DCI
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  8. ^ "FASS". Läkemedelsindustriföreningens Service AB. Archived from the original on 2011-10-01. Retrieved 2011-02-03.
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  16. ^ "Oxazepam Uses, Side Effects & Warnings - Drugs.com". drugs.com. Archived from the original on 2009-06-04.
  17. ^ "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September 2020. Retrieved 23 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
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  33. ^ "benzo.org.uk : Benzodiazepine Equivalence Table".
  34. ^ "Benzodiazepine equivalent dosage converter". GlobalRPH. Retrieved 2019-09-21.
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  42. ^ "List of psychotropic substances under international control" (PDF). Vienna Austria: International Narcotics Control Board. August 2003. Archived (PDF) from the original on 2005-12-05. Retrieved 2005-11-19.
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External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Oxazepam&oldid=1218627453"