Alprazolam toxicity

Adulteration, which can be accidental or deliberate, is another problem. Many herbal products have been found to contain prescription or OTC drugs and dangerous heavy metals. In 1998, for example, the California Department of Health reported that 32% of Asian herbal medicines sold in that state contained undeclared pharmaceuticals or heavy metals. A subsequent study of more than 500 Chinese herbal medicines found that about 10% of them contained undeclared drugs or toxic levels of metals. The FDA and other investigators have also detected sildenafil, colchicine, adrenal steroids, alprazolam, and other prescription drug ingredients in products claimed to contain only natural ingredients. 

American Psychiatric Association Benzodiazepine Dependence, Toxicity, and Abuse A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1990 Cohn JB, Wilcox CS Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients a double-blind study. J Clin Psychiatry 47 409 12, 1986 Dolovich LR, Addis A, Vaillancourt JM, et al Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and case-control studies. BMJ 317 839-843, 1998 Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184—1187, 1979 Kupfer DJ, Reynolds CF 111 Management of insomnia. N Engl J Med 336 341-346, 1997... 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

Compared with TCAs and MAOIs, BZDs have a rapid onset of action, have fewer unpleasant adverse effects, and are considerably less toxic. Despite these advantages, however, BZDs (with the possible exception of alprazolam, discussed later) generally appear devoid of true antidepressant effects. When the results of several well-controlled studies totalling 1,275 patients were summarized, the overall response to BZDs was 51% versus 73% for standard antidepressants. This generated a highly significant difference (p < 10 ) on the Mantel-Haenzsel test in favor of the antidepressants (Table 7-15). 

Verster JC, Volkerts ER. Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam a review of the literature. CNS Drug Rev. 2004 10 45-76. 

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. 

Isbister GK, O Regan L, Sibbritt D, Whyte IA. Alprazolam is relatively more toxic than other benzodiazepines in overdose. Br J Clin Pharmacol 2004 58(l) 88-95. 

DIGOXIN ANXIOLYTICS AND HYPNOTICS Alprazolam and possibly diazepam may t digoxin levels, particularly in the over-65s Uncertain at present Monitor digoxin levels watch for digoxin toxicity... 

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... 

An isolated report describes temazepam toxicity due to disulfiram. The serum levels of chlordiazepoxide and diazepam are increased by the use of disulfiram and some patients may possibly experience increased drowsiness. Alprazolam, oxazepam and lorazepam are either not affected, or only minimally affected, by disulfiram. 

Digoxin toxicity occurred in two elderly patients and rises in serum digoxin levels have been seen in others when they were given alprazolam. A reduction in the urinary clearance of digoxin has been described during the use of diazepam. No pharmacokinetic interaction seems to occur with digoxin and eszopiclone, zaleplon, or Zolpidem. 

Tollefson G, Lesar T, Grothe D, Garvey M. Alprazolam-ielated digoxin toxicity. AmJPsydd-atry 9ZA) A, 6 2- A. 

Developmental toxicity Acetohydroxamic acid Actmomycin D AU-trans retinoic acid Alprazolam Amikacin sulfate Aminoglutethimide Aminoglycosides Aminopterin... 

Carbamazepine levels are increased by CYP3A4 inhibitors (cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate) levels are decreased by CYP3A4 inducers (cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline). Carbamazepine may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity may decrease levels of phenytoin, warfarin, oral contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate may interfere with other anticonvulsants. 

---