Alcohol and diazepam

Kelly, T.H. et al., Performance-based testing for drugs of abuse dose and time profiles of marijuana, amphetamine, alcohol, and diazepam, J. Anal. Toxicol., 17, 264, 1993. 

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. 

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... 

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... 

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. 

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. 

Withdrawal from long-term high-dose use of alcohol or sedative-hypnotic drugs can be life threatening if physical dependence is present. Benzodiazepines, such as chlordiazepoxide Librium) and diazepam Valium), are sometimes used to lessen the intensity of the withdrawal symptoms when alcohol or sedative-hypnotic drug use is discontinued. Benzodiazepines are also employed to help relieve the anxiety and other behavioral symptoms that may occur during rehabilitation. 

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. 

Bo O, Hafner O, Langard O, et al. Ethanol and diazepam as causative agents in road accidents. In Iraelstam S, Lambert S, eds. Alcohol, drugs, and traffic safety. Toronto Addiction Research Foundation of Ontario, 1975. 

The NovaScan has received substantial testing in a number of laboratory and applied settings. Performance on the NovaScan has been demonstrated to be sensitive to the effects of alcohol, marijuana, diazepam, amphetamine, scopolamine, and an over-the-counter antihistamine.6 59 60 In addition, epidemiological differences in performance associated with gender, age, and occupation have been considered. Variations of the testing paradigm have been used in a number of commercial settings. 

Anton RF, Kranzler HR, McEvoy JP, Moak DH, Bianca R. A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal. Psychopharmacology (Berl) 1997 131(2) 123-9. 

In a multicenter, double-blind study, 310 patients with generalized anxiety disorder were treated for 6 weeks with abecarnil (mean daily dose 12 mg), diazepam (mean daily dose 22 mg), or placebo in divided doses for 6 weeks (11). Those who had improved at 6 weeks could volunteer to continue double-blind treatment for a total of 24 weeks. Slightly more patients who took diazepam (77%) and placebo (75%) completed the 6-week study than those who took abecarnil (66%). The major adverse events during abecarnil therapy were similar to those of diazepam, namely drowsiness, dizziness, fatigue, and difficulty in coordination. Abecarnil and diazepam both produced statistically significantly more symptom relief than placebo at 1 week, but at 6 weeks only diazepam was superior to placebo. In contrast to diazepam, abecarnil did not cause withdrawal symptoms. The absence of a placebo control makes it difficult to interpret the results of another study of the use of abecarnil and diazepam in alcohol withdrawal, which appeared to show comparable efficacy and adverse effects of the two drugs (12). 

A 50-year-old woman was referred to hospital for chronic depression with alcohol dependence (21). There was no history of drug allergy. She was given oral thioridazine 100 mg/day and diazepam 10 mg qds. After 2 days she noticed an erythematous eruption on her ankles. Thioridazine was withdrawn, but the eruption became more erythematous and affected both extremities and... 

One of the famous fathers of modern drug discovery, Leo Stembach, discovered and developed diazepam, which under its trade name Valium, became the first blockbuster dmg with sales exceeding 1 billion per year. It is also accused of unleashing a culture of quasi-accepted drug use for semirecreational use in anxiety-ridden mainstream America. The problem isn t so much in the drug itself, but problems arose from its interaction with alcohol and through its induction and development of both tolerance and dependence. 

One means of treatment for alcoholism is to give the addict a sedative/ relaxant drug such as diazepam for about seven days. After this time the worst of the unpleasant withdrawal symptoms will have receded. The patient still has to be kept away from alcohol and weaned off it, but the drug helps to reduce the craving. There are other newer drugs that also do this by increasing the substance GABA (see box above), they inhibit the activity of nerves in the brain that would otherwise increase when there is no alcohol present. 

In several cases the special nature of a formulation will preclude dilution by an aqueous infusion fluid. Injectable products containing phenytoin, digoxin and diazepam may come into this category if they are formulated in a nonaqueous but water-miscible solvent (such as an alcohol-water mixture) or as a solubilised (e.g. micellar) preparation. Addition of the formulation to water may result in precipitation of the dmg, depending on the final concentration of the dmg and solvent. It has been suggested that precipitation of the relatively insoluble diazepam may account for the high (3.5%) incidence of thrombophlebitis which occurs when diazepam is given intravenously. 

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