Triazolam toxicity

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

BZD hypnotics such as midazolam and triazolam are primarily metabolized via the P450 3A3/4 microenzyme system. Other BZDs often used as hypnotics, such as diazepam, can also be metabolized by CYP 33/4 and CYP 2C19. Any drugs that act as inhibitors or inducers of these isoenzymes could increase or decrease BZD levels, respectively (350). Thus, ketoconazole, macrolide antibiotics (e.g., erythromycin), SSRIs (e.g., fluoxetine-norfluoxetine and fluvoxamine), and other antidepressants (especially nefazodone) may decrease clearance and increase BZD levels to potentially toxic ranges. Conversely, rifampacin, CBZ, and dexamethasone may increase clearance and decrease BZD levels to potentially subtherapeutic ranges. 

Drugs metabolized by CYP that interact with cimetidine include, but are not limited to, the following lidocaine, quinidine, midazolam, triazolam, nifedipine, verapamil, and fentanyl (4). In each instance, inhibition of CYP by cimetidine results in reduced metabolic clearance and increases in serum concentrations of the other drug, which can lead to the expected toxicity and adverse experiences characteristic of the other drug. 

Although the shorter-acting BZs such as Xanax (alprazolam) and Halcion (triazolam) seem to be the most toxic and most prone to cause dependence, any BZ can cause these untoward effects, including the commonly used Klonopin (clonazepam) and Ativan (lorazepam). Overall, the BZs and many related medications used to treat anxiety and insomnia are potentially very brain disabling and spellbinding, and entail much graver risks than commonly recognized by health care providers and their patients. 

Kudo K, Imamura T, Jitsufuchi N, Zhang XX, Tokunaga H, Nagata T. Death attributed to the toxic interaction of triazolam, amitriptyline and other psychotropic drugs. Forensic Sci Int 1997 86(1-2) 35 11. 

CANNABIS ANXIOLYTICS AND HYPNOTICS-BZDs-alprazolam, diazepam, midazolam, triazolam Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

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. 

II. Toxic dose. In general, the toxic therapeutic ratio for benzodiazepines is very high. For example, oral overdoses of diazepam have been reported in excess of 15-20 times the therapeutic dose without serious depression of consciousness. On the other hand, respiratory arrest has been report after ingestion of 5 mg of triazolam and after rapid Intravenous injection of diazepam, midazolam, and many other benzodiazepines. Also, ingestion of another drug with CNS-depres-sant properties (eg, ethanol, barbiturates, opioids, etc) will likely produce additive effects. 

Liver cirrhosis increases the effects of cimetidine on the loss of chlo-rdiazepoxide. Confusion has been reported in a 50-year-old man taking clorazepate when he was given cimetidine, and increased sedation has been seen in some patients taking adinazolam and cimetidine. Prolonged hypnosis in an elderly woman and CNS toxicity (including lethargy and hallueinations) in a 49-year-old woman have been attributed to an interaction between triazolam and cimetidine but this remains unconfirmed. 

Britton ML, Waller ES. Central nervoussystem toxicity associated with concurrent use of triazolam and cimetidine. Drug Intell Clin Pharm (1985) 19,666-8. 

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