Clorazepate Alcohol

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. 

Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, hallucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepani, 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. 

Clorazepate Tranxene Oral Long 15-60 Anxiety disorders, alcohol withdrawal... 

Acute alcohol withdrawal For the symptomatic relief of acute alcohol withdrawal (clorazepate, chlordiazepoxide, oxazepam) may be useful in symptomatic relief of acute agitation, tremor, impending or acute delirium, tremens, and hallucinosis (diazepam). 

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. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Seizures Clonazepam [kloe NA ze pam] is useful in the chronic treatment of epilepsy, whereas diazepam is the drug of choice in terminating grand mal epileptic seizures and status epilepticus (see p. 149). Chlordiazepoxide [klor di az e POX ide], clorazepate [klor AZ e pate], diazepam, and oxazepam [ox A ze pam] are useful in the acute treatment of alcohol withdrawal. 

A 31-year-old man developed priapism after taking zuclopenthixol 30 mg/day for 8 days, the dose having been increased to 75 mg the day before, while he was still taking oral carbamazepine 600 mg/day and clora-zepate dipotassium 30 mg/day. He had a history of perinatal anoxic encephalopathy with severe motor sequelae and dyslalia, alcohol dependence, and a personality disorder. On the day before the priapism occurred, he had been physically restrained and given an extra dose of intramuscular clorazepate dipotassium 50 mg. When priapism occurred, all drugs except clorazepate were withdrawn and about 6 hours later the corpora cavernosa were washed and infused with noradrenaline in glucose (8 doses of 40 pg), after which the priapism resolved. 

Clinically important, potentially hazardous interactions with alcohol, anticholinergics, barbiturates, benzodiazepines, butabarbital, chloral hydrate, chlordiazepoxide, chlorpromazine, clonazepam, clorazepate, diazepam, ethchlorvynol, fluphenazine, flurazepam, hypnotics, lorazepam, MAO inhibitors, mephobarbital, mesoridazine, midazolam, narcotics, oxazepam, pentobarbital, phenobarbital, phenothiazines, phenylbutazone, primidone, prochlorperazine, promethazine, quazepam, secobarbital, sedatives, temazepam, thioridazine, tranquilizers, trifluoperazine, zolpidem... 

Clorazepate, a benzodiazepine derivative with antianxiety, anticonvnlsant, and sedative hypnotic properties (30 mg p.o. initially), is indicated in acute alcohol withdrawal and is used as an adjnnct in epilepsy (see also Table 9). 

Clorazepate is a benzodiazepine that potentiates action of GABA, an inhibitory neurotransmitter, resulting in increased neuronal inhibition and CNS depression, especially in limbic system and reticnlar formation. Clorazepate is indicated in the management of anxiety disorders relief of acnte alcohol withdrawal symptoms and adjunctive therapy in management of partial seizures. 

As well as the opioids cocaine and cannabis, polytoxicomane drug abusers also consume bromazepam, diazepam and flunitrazepam in high doses, and fatalities among drug abusers and substitution patients can often be blamed on the consumption of these substances, often in combination with alcohol [48]. Patients who suffer low-dose dependence, in addition to consuming the three above-named substances, also consume therapeutic amounts of dipotassium clorazepate, flurazepam, lorezepam, nitrazepam or oxazepam, sometimes also in combination with amphetamines or antihistamines. 

It is very difficult to assess and compare the results of the very many studies of this interaction because of the differences between the tests, their duration, the dosages of the benzodiazepines and alcohol, whether given chronically or acutely, and a number of other variables. However, the overall picture seems to be that benzodiazepines and related drugs including diazepam, " alprazolam,bromazepam, brotizolam, chlo-rdiazepoxide, " clobazam, dipotassium clorazepate, flunitrazepam, flurazepam, loprazolam, " lorazepam, lormetazepam, medazepam, midazolam, nitrazepam, " " oxazepam, temazepam, " triazolam, and zopiclone enhance the effects of alcohol i.e. cause increased drowsiness, impaired performance and driving skills. 

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