Triazolam Alcohol

Ator NA, Weerts EM, Kaminski BJ, et al Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons. Drug Alcohol Depend 61 69-84, 2000... 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

Most sedative drugs, including narcotics and alcohol, potentiate the sedative effects of benzodiazepines. In addition, medications that inhibit hepatic cytochrome P450 (CYP) 3A3/4 increase blood levels and hence side effects of clonazepam, alprazolam, midazolam, and triazolam. Lorazepam, oxazepam, and temazepam are not dependent on hepatic enzymes for metabolism. Therefore, they are not affected by hepatic disease or the inhibition of hepatic enzymes. 

Triazolam potentiates the CNS depressant effects of phenothiazines, narcotics, antihistamines, MAOIs, barbiturates, alcohol, general anesthetics, and antidepressants. Use with cimetidine and disulfiram may increase triazolam s plasma concentration. 

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a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn.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. 

Fatalities due to acute BZD overdose alone are extremely rare. Nevertheless, fatal overdoses with triazolam in the elderly have been reported ( 192, 193). Even with ingestion of massive doses, recovery appears to be rapid and without serious complications or aftereffects ( 194, 195, 196 and 197). Combined ingestion of BZDs with other CNS depressants (alcohol, barbiturates, narcotics, orTCAs), however, may result in severe CNS and respiratory depression or hypotension. Severity of symptoms appears to depend more on the type and quantity of the other drugs than on the BZD plasma level (194, 195, 196 and 197). 

Seizures have been reported after withdrawal of high doses of triazolam or relatively low doses combined with alcohol ( 347, 348 and 349). The FDA has reported a signal of an association for withdrawal seizures associated with triazolam ( 350). In a chart review of 150 consecutive patients withdrawn from BZDs, three of 25 triazolam patients experienced seizures, compared with two of 125 given other BZDs ( 351). Psychosis with delirium also has been reported after discontinuation of high triazolam doses (352). 

S toops, W.W. and Rush, C.R., Differential effects in humans after repeated administrations of zolpidem and triazolam, Am. J. Drug Alcohol Abuse, 29, 281, 2003. 

Roache, J.D., Spiga, R., and Burt, D.B., Triazolam and ethanol effects on human matching-to-sample performance vary as a function of pattern size and discriminability, Drug Alcohol Depend., 32, 219, 1993. 

BZDs such as chlordiazepoxide (Librium) or diazepam (Valium) may be prescribed to treat anxiety, seizures, acute stress reactions, and panic attacks, or to alleviate the side effects of drug or alcohol withdrawal. Those BZDs with a more sedating effect, such as estazo-lam (ProSom) or triazolam (Halcion), may be prescribed for short-term treatment of sleep disorders. However, the newer generation of non-BZD agents—zolpidem (Ambi-en) and (Sonata)—are less potentially addictive hypnotic drugs than the BZDs. 

KuitunenT, MattilaMJ, SeppalaT (1990) Actions and interactions of hypnotics on human performance single doses of zopiclone, triazolam and alcohol. Int ClinPsychopharmacol 5 (Suppl 2) 115-130... 

Division of Epidemiology and Surveillance, Office of Epidemiology and Biostatistics. (1990, March 20). Memorandum Increased frequency report Triazolam deaths, interaction with alcohol, and CNS depression. Rockville, MD Center for Drug Evaluation and Research, Food and Drug Administration. 

The effects of alcohol combined with either zaleplon or triazolam have been studied in 18 healthy volunteers (21). Triazolam, with and without ethanol, impaired digit symbol substitution, symbol copying, simple and complex reaction times, and divided attention performance compared with placebo. Zaleplon without ethanol impaired only digit symbol substitution and divided attention tracking, but when it was combined with ethanol all measures were impaired. However, zaleplon without ethanol was consistently better than triazolam alone. Zaleplon produced less performance impairment and a shorter period of ethanol potentiation than triazolam. 

Despite common actions upon GABA, no pharmacodynamic or pharmacokinetic interations have been shown when tiagabine is combined with the benzodiazepine triazolam or with alcohol... 

Triazolam, USP. Triazolam. 8-chloro-6-(o-chlorophc-nyl)-l-methyl-4Ay-j-triaz.olol4.3-a f l,4 benzxxliazcpinc (Hal-cion). has all of the characteristic benzodiazepine pharmacological actions. It is marketed as a sedative-hypnotic drug said to impair little, if any. daytime function. It is rapidly metabolized to the I-methyl alcohol, which is then conjugated and excreted. 

Triazolam is contraindicated in patients in coma, because the drug s hypnotic or hypotensive effect may be prolonged or intensified in pregnant patients, because it may be feto-toxic and in patients with acute alcohol intoxication who have depressed vital signs, because the drug will worsen CNS depression. 

Benzodiazepine and related hypno-sedatives increase the CNS depressant effects of alcohol to some extent. The risks of car driving and handling other potentially dangerous machinery are increased. The risk is heightened because the patient may be unaware of being affected. Some benzodiazepines used at night for sedation are still present in appreciable amounts the next day and therefore may continue to interact. Alcohol may also increase the plasma levels of brotizolam, clobazam, diazepam, and possibly triazolam, whereas alprazolam may increase blood-alcohol levels. Alcohol has been reported to increase aggression or amnesia and/or reduce the anxiolytic effects of some benzodiazepines. 

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. 

Some of the benzodiazepines and related drugs that are used primarily to aid sleep, such as flunitrazepam, flurazepam, "" "" nitrazepam, " and temazepam, when taken the night before alcohol or in the evening with alcohol, can still interact with alcohol the next morning. However, midazolam,- loprazolam, lormetazepam, triazolam, Zolpidem, and zopiclone have been reported not to do so. The sedative effects of midazolam alone, and midazolam with fenta-nyl have been shown to have dissipated within 4 hours, and to not be affected by alcohol after this time. However, some patients may metabolise midazolam more slowly and so an interaction could still be possible, especially in older patients or those receiving additional drugs. ... 

Several studies have reported that alcohol increases plasma levels of diazepam and that alcohol accelerates the absorption of diazepam, but others have suggested that alcohol has no significant effect on diazepam pharmacokinetics. Plasma levels of brotizolam and clobazam may be increased by alcohol. One study reported that the plasma levels of triazolam were increased by alcohol, but other studies have found only a minimal pharmacokinetic interaction. However, an in vitro study demonstrated that alcohol inhibited the metabolism of triazolam by the cytochrome P450 isoenzyme CYP3A. Another in vitro study reported that the formation of flunitrazepam metabolites was weakly inhibited by alcohol, but a pharmacokinetic study suggested that there was no interaction. Alcohol appears to have minimal effects on the pharmacokinetics of alprazolam, and zopiclone. ... 

Mendelson WB, Goodwin DW, Hill SY, Reichman JD. The morning after residual EEG effects of triazolam and flurazepam, alone and in combination with alcohol. Curr TherRes Clin Exp (1976) 19, 155-63. 

Psychological The potential effects of triazolam on cognitive performance have been studied in a double-blind, placebo-controlled comparison of the acute effects of triazolam and alcohol in 20 social drinkers [15 ]. Triazolam was more likely to impair several objective measures of cognitive performance, such as episodic memory and divided attention, and it also slowed performance across several cognitive measures. Triazolam alone impaired other measures of metacognition, such as error detection on a choice reaction time task. 

Kleykamp BA, Griffiths RR, Mintzer MZ. Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers. Exp Clin Psychopharmacol 2010 18(1) 1-16. 

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