Benzodiazepine clorazepate

The rates of oral absorption of sedative-hypnotics differ depending on a number of factors, including lipophilicity. For example, the absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration. 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Benzodiazepines have a low risk for abuse in anxiety disorder patients without a history of alcohol or other substance abuse. Among the benzodiazepines there may be a spectrum of abuse liability, with drugs that serve as prodrugs for desmethyldiazepam (e.g., clorazepate), slow-onset agents (e.g., oxazepam), and partial agonists (e.g., abecarnil) having the least potential for abuse. However, there is no currently marketed benzodiazepine or related drug that is free of potential for abuse. 

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

Benzodiazepines alprazolam bromazepam clorazepate dipotassium diazepam... 

Benzodiazepines [P] Decreased metabolism of alprazolam, chlordiazepoxide, diazepam, halazepam, prazepam, and clorazepate but not oxazepam, lorazepam, or temazepam. 

Benzodiazepines exert central depressant effects on spinal reflexes, in part mediated by the brainstem reticular system.3 For example, chlordiazepoxide depresses the duration of electrical after-discharge in the limbic system. Most benzodiazepines elevate the seizure threshold and therefore may be used as anticonvulsant medications. Diazepam, clonazepam, and clorazepate may be prescribed for this therapeutic purpose. 

Several members of the benzodiazepine group are effective in treating epilepsy, but most are limited because of problems with sedation and tolerance. Some agents such as diazepam (Valium) and lorazepam (Ativan) are used in the acute treatment of status epilepti-cus (see Treatment of Status Epilepticus ), but only a few are used in the long-term treatment of epilepsy. Clonazepam (Klonopin) is recommended in specific forms of absence seizures (e.g., the Lennox-Gastaut variant) and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate (Tranxene) is another benzodiazepine that is occasionally used as an adjunct in certain partial seizures. 

Benzodiazepines Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Lorazepam (Ativan) Potentiate inhibitory effects of GABA... 

Benzodiazepines are classified according to how long their effects last and by their potency. The ultra-short acting benzodiazepines include midazolam (Versed) and triazolam (Halcion) the short-acting benzodiazepines include alprazolam (Xanax) and lorazepam (Ativan) the long-acting include chlordiazepoxide (Librium) and diazepam (Valium). High potency benzodiazepines include alprazolam, lorazepam, triazolam, and clonazepam (Klonopin). Low-potency benzodiazepines include chlordiazepoxide, clorazepate (Tranxene), diazepam, and flurazepam (Dalmane). 

OFFICIAL NAMES Minor tranquilizers (sedative-hyp-notics/anxiolytics)/Benzodiazepines Alprazolam (Xanax) chlordiazepoxide (Librium, Novopoxide) clonazepam (Klonopin) clorazepate (Azene, Tranxene) diazepam (Valium) estazolam (ProSom) flunitrazepam (Rohypnol/illegal in the United States) flurazepam (Dalmane) halazepam (Paxipam) lorazepam (Ativan) midazolam (Versed) oxazepam (Serax) prazepam (Centrax) quazepam (Doral) temazepam (Restoril) triazolam (Halcion)... 

Benzodiazepine (BZ) intoxication is manifested as slurred speech, poor coordination, swaying, drowsiness, hypotension, nystagmus, and confusion. Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, haJlucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepam, alprazolam) has an onset within 12 to 24 hours of the last dose. Diazepam, chlordiazep-oxide, and clorazepate have elimination half-lives (or active metabolites with elimination half-lives) of 24 to greater than 100 hours. So, withdrawal may be delayed for several days after their discontinuation. Sedative-hypnotic dependence is summarized in Table 73-2. 

Fig. 3. Separation of some benzodiazepines using System HI. A, clorazepic acid B, nitrazepam C, clobazam D, oxazepam E, temazepam F, chlordiazepoxide G, diazepam H,...

Nordazepam is a metabolite of several benzodiazepines including chlordiazepoxide, clorazepate, diazepam, medazepam, and prazepam. 

Figure 18-6. UPLC chromatography of benzodiazepines on a 14.5-cm x 50- xm column packed with l- xm polybutadiene-encapsulated non-porous zirconia particles. Eluent pH 7 buffer-acetonitrile 68 22 at 100°C. Peaks 1, uracil 2, clorazepate 3, fluni-trozepam 4, clonazepam 5, chlordiazepoxide 6, oxazepam 7, clorazepate 8, diazepam. (Reproduced from reference 53, with permission from Elsevier.)...

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