The metabolism of lorazepam is different than other benzodiazepines as it is metabolized in the liver by the process of glucuronidation. There are two other benzodiazepines metabolized in this fashion and they are temazepam and oxazepam.
Powlovich, MD. Defined by: Lauren G.
Lorazepam is a benzodiazepine that works through activation of GABAA to increase the activity of GABA which in turn reduces neuronal firing in the brain.
International Anesthesia Research Society.
Filed Under: 2015 Keywords (Defined), ABA Keyword Categories, Basic, L, Pharmacology.
OpenAnesthesia content is intended for educational purposes only and not intended as medical advice.
Reuse of OpenAnesthesia content for commercial purposes of any kind is prohibited.
Glucuronidation is when a glucuronic acid is added to a substrate from UDP-glucuronic acid via a UDP glucuronosyltransferase. General 47%/2015. The useful pneumonic “LOT” can help you to remember which benzodiazepines are metabolized through glucuronidation. The interesting and important fact about the benzodiazepines that are metabolized through glucuronidation is that there are no active metabolites and they are rarely susceptible to drug-drug interactions unlike other benzodiazepines such as midazolam and diazepam that are metabolized through the Cytochrome P450 (microsomal oxidation) pathway and potentially have many more drug-drug interactions. The metabolism of lorazepam is different than other benzodiazepines as it is metabolized in the liver by the process of glucuronidation. There are two other benzodiazepines metabolized in this fashion and they are temazepam and oxazepam.
Drug Test Anal. 2011 Oct;3(10):695-704. doi: 10.1002/dta.305. Epub 2011 Aug 12. Metabolites of lorazepam: Relevance of past findings to present day use of.
Generate a file for use with external citation management software.
National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA. National Center for Biotechnology Information, U.S.
Following lorazepam administration (2 mg, p.o.) to 6 volunteers, metabolites were identified in urine by electrospray ionization LC-MS/MS, aided by the use of deuterated analogues generated by microsomal incubation for use as internal chromatographic and mass spectrometric markers. The quinazolinone, and particularly the quinazoline carboxylic acid metabolite, provided longer detection windows than lorazepam in urine extracts not subjected to enzymatic hydrolysis, a finding that is highly relevant to toxicology laboratories that omit hydrolysis in order to rapidly reduce the time spent on gas chromatography-mass spectrometry (GC-MS) analysis. The advent of liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the sensitivity it confers, permits the analysis of both phase I and II drug metabolites that in the past would have been difficult to target using other techniques. Metabolites present were lorazepam glucuronide, a quinazolinone, a quinazoline carboxylic acid, and two hydroxylorazepam isomers, one of which is novel, having the hydroxyl group located on the fused chlorobenzene ring. These metabolites may have relevance to current analytical toxicology employing LC-MS/MS, and lorazepam was chosen as a model drug for investigation, as only the parent compound has been targeted for screening purposes. With hydrolysis, the longest windows of detection were achieved by monitoring lorazepam, supporting the targeting of the aglycone with free drug for those incorporating hydrolysis in their analytical toxicology procedures.
Name: Lorazepam; Accession Number: DB00186 (APRD00116) Lorazepam, a benzodiazepine not transformed to active metabolites.
For the management of anxiety disorders, and for treatment of status epilepticus.
This is an inactive metabolite and is eliminated mainly by the kidneys. Lorazepam is hepatically metabolized and is extensively conjugated to the 3-0-phenolic glucuronide.
The percent of administered dose recovered in urine as lorazepam glucuronide was 74±4%. When a single 2 mg oral dose is give to healthy subjects, 88±4% of the administered dose was recovered in urine and 7±2% was recovered in feces. Only 0.3% of the dose was recovered as unchanged lorazepam, and the remainder of the radioactivity represented minor metabolites.
Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS.
Lorazepam is an alternative water-soluble agent that is well absorbed after both oral. It is one of the few benzodiazepines not possessing active metabolites.
Pregnancy category D Lactation Possibly unsafe Metabolism Liver Excretion Urine, half-life 14 hr DEA schedule IV Read full chapter.
The largest dose should be taken 1 hour before bedtime. The safety and efficacy of lorazepam in patients younger than 12 years have not been established (as is true for most drugs). For anxiety the initial dose is from 2 to 3 mg per day in two to three doses. For preoperative anxiety control or as an aid to sleep before dental or surgical treatment, a single dose of 2 to 4 mg may be given 1 hour before sleep or 1 hour before the appointment.
As with most benzodiazepines, lorazepam therapy has not been associated with serum Lorazepam is metabolized by the liver to inactive metabolites and is.
Drug Class: Sedatives and Hypnotics, Benzodiazepines.
As with most benzodiazepines, lorazepam therapy has not been associated with serum aminotransferase or alkaline phosphatase elevations, and clinically apparent liver injury from lorazepam has not been reported and must be very rare, if it occurs at all. Background. Lorazepam is an orally available benzodiazepine used widely in the therapy of anxiety and insomnia.