Flurazepam elimination

There is an association between falls and hip fractures and the use of long-elimination half-life benzodiazepines thus, flurazepam and quazepam should be avoided in the elderly. 

The benzodiazepines that have been most commonly marketed as sedative-hypnotics include temazepam (Restoril), estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), and triazolam (Halcion). Of these five, temazepam is the most easily metabolized and eliminated. Therefore, temazepam is preferred for elderly and medically ill patients to minimize the risk of drug accumulation. 

BZDs with active metabolites and slow elimination, such as diazepam, flurazepam, and quazepam, are well known for producing unwanted daytime sedation (111,... 

Flurazepam (Dalmane) 0.5-1.0 Long Long elimination half-life because of active metabolites... 

The less potent and more slowly eliminated drugs (flurazepam and quazepam) continue to improve sleep even after discontinuation. 

The choice of a particular benzodiazepine is based on its pharmacokinetic profile. When used as a single dose, the extent of distribution and elimination half-life is important in predicting the duration of action. However, after multiple dosing, the elimination half-life and formation of active metabolites determine the extent of drug accumulation and resultant clinical effects." The benzodiazepine pharmacokinetic profiles are summarized in Table 71-4. The onset of action depends on the rate of absorption. Flurazepam and triazolam are absorbed rapidly. Temazepam is less lipophilic and has a slower onset of effect. Sedation after flurazepam, estazolam, and quazepam occurs within 1 to 2 hours after ingestion." Triazolam is redistributed quickly because of its high lipophilicity and thus has a short duration of effect." Estazolam and temazepam are intermediate in their duration of action. The therapeutic effects of flurazepam and quazepam are long in comparison because of the active metabolites. 

A-DAF accounts for most flurazepam pharmacologic effects. Quazepam and one of its metabolites, 2-oxo-quazepam, have elimination half-lives of 39 hours." Quazepam s oxo-quazepam metabolite is metabolized to A-DAF. If oxidation of A-DAE is impaired its half-life becomes prolonged, and complications of drug accumulation may result with repeated dosing however, tolerance may develop to these effects. A-DAE may be useful when daytime anxiety or early morning awakening are complaints, but daytime sedation and impaired psychomotor performance may complicate therapy. ... 

The incidence of CNS side effects increases with age secondary to prolonged benzodiazepine half-lives, which may increase the potential for drug accumulation. Prolonged sedation and cognitive and psychomotor impairment are concerns in the elderly. Drugs with short and intermediate elimination half-lives are associated with fewer performance deficits however, they may be associated with more daytime anxiety in elderly patients. There is an association between falls and hip fractures and the use of benzodiazepines with long elimination half-lives thus flurazepam and quazepam should be avoided in elderly patients. ... 

With an understanding of the mechanisms and metabolic reactions of these drugs, newer drug design concepts were applied in later synthetic phases. It is not surprising that compounds were developed in which certain pharmacologic properties became elevated or subdued (but never eliminated). Flurazepam (No. 7, Table 12-8), nitrazepam (No. 13), and triazolam (No. 22) became widely used as hypnotics clonazepam (No. 3) is used almost exclusively as an anticonvulsant, while diazepam (No. 6), clorazepate (No. 4), lorazepate (No. 19), prazepam (No. 16), and aprazolam (No. 19) are marketed primarily as anxiolytics. 

Drugs active at the benzodiazepine receptor may be divided into four categories based on their elimination half-lives (1) ultrashort acting (2) short-acting (tj <6 hours) triazolam, the nonbenzodiazepine Zolpidem (tj 2 hours), and zopiclone (tj = 5 hours) (3) intermediate-acting 24 hours) estazolam and temazepam-, and (4) long-acting (tj >24 hours) flurazepam, diazepam, and quazepam. 

The pharmacokinetic profile for each of the benzodiazepines is shown in Table 19.1. The benzodiazepines that are slowly eliminated or are metabolized to slowly eliminated active metabolites can be used as hypnotics. For example, flurazepam is primarily metabolized by ... 

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