Lorazepam metabolic pathways

Knowing the structure of a particular BZ drug can help predict the metabolic pathway for that drug. For example, oxazepam, lorazepam, and temazepam are all 3-OH BZs and are directly conjugated (Chouinard et ah, 1999). Temazepam is partly demethylated to oxazepam, but otherwise these drugs have no active metabolites (Bellantuono et ah, 1980). 

Oxazepam (6) is formed during the metabolism of many other benzodiazepines, but its own metabolic profile is relatively simple. Like lorazepam, the major metabolic pathway is glucuronidation at the 3-hydroxy group followed by urinary excretion. Up to 80% of the dose is recovered from the urine as the glucuronide. The mean half-life of oxazepam is approximately 9 h (98). 

Disulfiram inhibits the initial metabolism (A-demethylation and oxidation) of both chlordiazepoxide and diazepam by the liver so that an alternative but slower metabolic pathway is used. This results in the accumulation of these benzodiazepines in the body. In contrast, the metabolism (glucuronidation) of oxazepam and lorazepam is minimally affected by disulfiram so that their clearance from the body remains largely unaffected. The possible interaction between disulfiram and temazepam is not understood, as temazepam is also mainly eliminated in the urine as the inactive glucuronide metabolite, and so its metabolism would not be expected to be affected by disulfiram. 

Lorazepam, oxazepam and temazepam are metabolised by a different metabolic pathway involving glucuronidation, which is not affected by cimetidine, and so they do not usually interact. 

Metabolic pathways, drug clearance and elimination (Lorazepam)... 

Disulfiram inhibits CYP enzymes 1A2, 2C9, and 3A4 many benzodiazepines are metabolized via these pathways lorazepam, temazepam, and oxazepam are NOT metabolized via the CYP4S0 system and are reasonable alternatives. 

The BZs are all metabolized in the liver via the hepatic cytochrome P450 (CYP) enzymes through one or both of the following pathways phase I oxidation and dealkylation, and/or phase II conjugation to glucuron-ides, sulfates, and acetylated compounds. Diazepam, chlordiazepoxide, and flurazepam all undergo both phase 1 and phase 11 metabolism. Lorazepam, lorme-tazepam, oxazepam, and temazepam are all metabolized by phase 11 alone and are better tolerated by patients with liver impairment. 

The metabolism of lorazepam (e.g., Ativan), oxazepam (e.g., Serax), and temazepam (e.g., Restoril) are not likely to be affected, and one of these agents may be preferred when a benzodiazepine is indicated in a patient being treated with cimetidine. The experience with ranitidine (e.g., Zantac), famotidine (Pepcid), and nizatidine (Axid) suggests that these agents are not likely to inhibit hepatic enzyme systems, and these other histamine H2-receptor antagonists are less likely than cimetidine to interact with other drugs that are metabolized via these pathways. 

A combination of paracetamol (acetaminophen) plus codeine is especially well suited to post-peel pain, but should not be used in the hours following a phenol peel, as paracetamol (a phenol derivative) goes through the same detoxification pathways as phenol, which could create metabolic competition and the risks of toxicity associated with phenol might be increased. Preventive administration of benzodiazepines (lorazepam 2.5 mg before the peel and on the night of the peel before going to bed) relieves the anxiety caused by these unpleasant sensations and reduces the need for analgesics after the peel. In case of very severe, localized pain (extremely rare), a nerve block could be used. 

Elimination of lorazepam occurs by metabolism within the hver and renal excretion of the metabolites. Glucuronidation to form lorazepam-glucuronide is the major pathway for metabolism. Minor metabolites include a hydroxylated derivative, a quinazolinone derivative and a quinazoline carboxylic acid. Seventy... 

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