Diazepam Alcohol

Mirtazepine + diazepam, alcohol —> increased sedation and possible cognitive impairment. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

Some of these drugp may have additional uses as sedatives, muscle relaxants, anticonvulsants, and in the treatment of alcohol withdrawal. For example, clo-razepate (Tranxene) and diazepam (Valium) are used as anticonvulsants (see Chap. 28). Additional uses of the individual antianxiety drugp are given in the Summary Drug Table Antianxiety Drugp. 

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. 

Bailly D, Servant D, Blandin N, et al Effects of beta-blocking drugs in alcohol withdrawal a double-blind comparative study with propranolol and diazepam. Bio-med Pharmacother 46 419—424, 1992... 

Carlsson C, Fasth BG A comparison of the effects of propranolol and diazepam in alcoholics. Br J Addict Alcohol Other Drugs 71 321-326, 1976... 

Cowley DS, Roy-Byrne PP, Radant A, et al Eye movement effects of diazepam in sons of alcoholic fathers and male control subjects. Alcohol Clin Exp Res 18 324—332, 1994... 

Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184-1187, 1979 Goldman D Recent developments in alcoholism genetic transmission. Recent Dev Alcohol 11 231-248, 1993... 

Iwata N, Cowley DS, Radel M, et al Relationship between a GABA alpha g Pro385Ser substitution and benzodiazepine sensitivity. Am] Psychiatry 156 1447—1449,1999 Jacobson AF, Dominguez RA, Goldstein B, et al Comparison of buspirone and diazepam in generalized anxiety disorder. Pharmacotherapy 5 290—296, 1985 Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Ciraulo DA, Sands BE, Shader RI Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 145 1501-1506, 1988b Ciraulo DA, Barnhill JG, Ciraulo AM, et al Parental alcoholism as a risk factor in benzodiazepine abuse a pilot smdy. Am J Psychiatry 146 1333-1335, 1989 Ciraulo DA, Antal EJ, Smith RB, et al The relationship of alprazolam dose to steady-state plasma concentrations. J Clin Psychopharmacol 10 27—32, 1990 Ciraulo DA, Sarid-Segal O, Knapp C, et al Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry 153 956-958, 1996 Ciraulo DA, Barnhill JG, Ciraulo AM, et al Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 37 64-73, 1997... 

Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Sellers EM, Naranjo CA, Harrison M, et al Diazepam loading simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 34 822-826, 1983 Sharp CW Introduction to inhalant Abuse, in Inhalant Abuse A Volatile Research Agenda (NIDA Research Monograph 129). Edited by Sharp CW, Beuvais F, Spence R. Rockville, MD, National Institute on Drug Abuse, 1992, pp 1-10 Smelson DA, Losonczy MF, Davis CW, et al Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence. Can J Psychiatry 47 671-675, 2002... 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

In contrast to chlordiazepoxide and diazepam, lorazepam and oxazepam are not metabolized into active compounds in the liver. Instead, they are excreted by the kidneys following glucuronidation. This is important because many alcohol-dependent patients have compromised liver function. Therefore, when treatment is initiated before the results of blood tests for liver function are known, as is often the case in outpatient clinics, lorazepam and oxazepam may be preferred. Patients with liver disease may still be treated with diazepam and chlordiazepoxide, but at lower doses. This can be accommodated with the loading technique, although hourly dosing with 5 mg of diazepam or 25 mg of chlordiazepoxide may be sufficient. 

The answer is k. (Katzung, p 390.) Long-acting benzodiazepams such as diazepam are useful in alcohol withdrawal. Its active metabolite is eliminated slowly, thereby increasing its duration of action In patients with... 

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. 

Diazepam Valium Oral, IV Long 4-40 Anxiety disorders, alcohol withdrawal... 

Benzodiazepines. Like the barbiturates, benzodiazepines bind to the GABA receptor and are therefore cross-tolerant with alcohol. As a result, they also make suitable replacement medications for alcohol and are widely used for alcohol detoxification. Theoretically, any benzodiazepine can be used to treat alcohol withdrawal. However, short-acting benzodiazepines such as alprazolam (Xanax) are often avoided because breakthrough withdrawal may occur between doses. Intermediate to long-acting benzodiazepines including chlordiazepoxide (Librium), diazepam (Valium), oxazepam (Serax), lorazepam (Ativan), and clonazepam (Klonopin) are more commonly utilized. 

Concomitant administration of methotrexate and Voltarol, a proprietary preparation of diclofenac, a non-steroidal anti-inflammatory drug, may result in accumulation of methotrexate as its excretion is reduced. The use of diclofenac and diuretics such as bendroflumethiazide may increase the risk of nephrotoxicity. Concomitant use of alcohol and an angiotensin-converting enzyme inhibitor such as lisinopril (Zestril) may result in an enhanced hypotensive effect. Alcohol and the benzodiazepine diazepam (Valium) may result in enhanced sedation. 

All benzodiazepines are indicated in obsessive compulsive disorders. Diazepam and lorazepam are effective in status epilepticus, whereas chlordiazepoxide is indicated in alcohol withdrawal. 

Diazepam is used for the control of anxiety and tension, the relief of muscle spasms, and the management of acute agitation during alcohol withdrawal, but it itself may be habit-forming. Chlordiazepoxide has similar uses and its synthesis is somewhat analogous to diazepam. Flurazepam is a hypnotic, useful for insomnia treatment. It is reported to provide 7-8 hr of restful sleep. 

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). 

There is no evidence from randomized trials that general strategies to prevent delirium are successful. Benzodiazepines are significantly better than placebo in preventing delirium and seizures due to alcohol withdrawal, and long-acting benzodiazepines (such as diazepam) are more effective than... 

Management of methanol and ethylene glycol poisoning is similar. Symptomatic support of respiration and circulation is augmented by correction of metabolic acidosis with intravenous bicarbonate infusion, and control of seizures with diazepam. Ethanol inhibits the metabolism of methanol and ethylene glycol to the toxic metabolites, and can give time for further treatment. The goal is to maintain blood ethanol concentrations between 100 and 150 mg per decilitre, sufficient to saturate alcohol... 

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