Alprazolam

Sample preparation 2 mL Whole blood or plasma + 2 mL buffer + 5 mL chloroform isopropanol n-heptane 60 14 26, shake gently horizontally for 10 min, centrifuge at 2800 g for 10 min. Remove the lower organic layer and evaporate it to dryness under vacuum at 45°, reconstitute the residue in 100 jjlL mobile phase, centrifuge at 2800 g for 5 min, inject a 50 jlL aliquot of the supernatant. (Buffer was saturated ammonium chloride solution 25% diluted with water, adjusted to pH 9.5 with 25% ammonia solution.) 

Mobile phase MeOH THF buffer 65 5 30 (Buffer was 0.68 g/L (10 mM (sic)) KH2PO4 adjusted to pH 2.6 with concentrated orthophosphoric acid.) (At the end of each session wash the column with water for 1 h and MeOH for 1 h, re-equilibrate for 30 min.) 

Interfering cycloguanil, debrisoquine, ketamine, lorazepam, methaqualone, metoprolol, nifedipine, piroxicam, sulindac 

Tracqui, A. Kintz, R Mangin, P. Systematic toxicological analysis using HPLC/DAD. J.Forensie Sci., 1995, 40, 254-262 

Sample preparation 50 q,L Serum -i- 25 xL 0.5 p.g/mL demoxepam in water -i- 100 (jiL 1 M pH 9.0 borate buffer, mix well, add 2 mL diethyl ether, vortex for 40 s, centrifuge at 1100 g for 5 min. Remove ether layer and evaporate it at 40° under nitrogen. Take up residue in 50 pL mobile phase, inject an aliquot. 

Chemicel Name 8-Chloro-1 methyl-6-phenyl-4H-s-triazolo[4,3-a] [1,4]benzodiazepine Common Name — 

Trads Name Manufacturer Country Year Introdi 

6- Chloro-2-hydrazino-4-phenylquinoline A stirred mixture of 2,6-dichloro-4-phenylquino-line 12.7 g,0.01 mol) and hydrazine hydrate (6.8 g) was refluxed under nitrogen for 1 hour and concentrated in vacuo. The residue was suspended in warm water, and the solid was collected by filtration,dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81 g (67% yield) of 6 hloro-2-hydrazino-4-phenylquinollne of melting point 1565°-157°C. 

7- Chloro-1 -methyl-5-phenyl-s-trizolo[4,3-a]quinoline A stirred mixture of 6 hloro-2-hy-drazino-4-phenylquinoline (1.4 g,0.0052 mol),triethyl-orthoacetate (0.925 g,0.0057 mol) and xylene (100 ml) was refluxed, under nitrogen, for 2 hours 40 minutes. During this period the ethanol formed in the reaction was removed by distillation through a short,glass helix-packed column. The mixture was concentrated to dryness In vacuo and the residue was crystallized from methanol-ethyl acetate to give 1.28 g of 7-chloro-1-methyl-5-phenyl-s-triazolo[4,3-a]-quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride methanol and had a melting point 252.5°-253.5°C. 

5-Chloro-2-(3-methyl-4H-1,2,4-triazol-4-yDbenzophenone (Oxidation of 7 hloro-1 -methyl-5-phenyl-s-trizolo[4,3-alquinoline) A stirred suspension of 7 hloro-1-methyl-5-phenyl-s-tri-azolo[4,3-a] quinoline (294 g, 0.01 mol) In acetone (110 ml) was cooled in an ice-bath and treated slowly with a solution prepared by adding sodium periodate (2 g) to a stirred suspension of ruthenium dioxide (200 mg) in water (35 ml). The mixture became dark. Additional sodium periodate 18 g) was added during the next 15 minutes. The ice-bath was removed and the mixture was stirred for 45 minutes. Additional sodium periodate (4 g) was added and the mixture was stirred at ambient temperature for 18 hours and filtered. The solid was washed with acetone and the combined filtrate was concentrated in vacuo. The residue was suspended in water and extracted with methylene chloride. The extract was dried over anhydrous potassium carbonate and concentrated. The residue was chromatographed on silica 

Molecular formula C,7H,3CIN4 Molecular weight 308.8 CAS Regletry No. 28981-97-7 

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Benzodiazepines, ie, the hiU BZR agonists, are prescribed for anxiety, insomnia, sedation, myorelaxation, and as anticonvulsants (97). Those benzodiazepines most commonly prescribed for the treatment of anxiety disorders are lorazepam (19), alprazolam (20), diazepam (21), bromazepam (22), chlorazepate (23), and oxazepam (24). These dmgs together represent about 70% of total... 

VALIDATED HPTLC DETERMINATION AND CONTENT UNIFORMITY TEST FOR ALPRAZOLAM AND MELATONINE IN TABLET DOSAGE FORM... 

A simple, rapid, precise and economical High Performance Thin Layer Chromatographic (HPTLC) method has been developed and validated for determination of Alprazolam and Melatonine in its pharmaceutical preparation. It was performed on silica gel 60 Thin Layer... 

Ms. Stovall, age 66 years, is hospitalized for congestive heart failure. She is improving but has been complaining offeelings of anxiety. Her respirations are 32 min, heart rate 88 bpm, and blood pressure 118 j60 mm Hg. The primary health care provider prescribes alprazolam 0.25 mg PO TID. What precautions would the nurse expect to be taken because of Ms. Stovall s age Discuss what assessment findings would indicate increased anxiety. 

CfiHfiClN 106-47-8) see Acetarsol Alprazolam Diazepam Efavirenz Flunitrazepam Flutoprazepam Medazepam Quazepam... 

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. 

Medical use of benzodiazepines has been declining. Prescribing trends show an overall decline in the number of all benzodiazepine prescriptions written, with a market shift to increased prescribing of short elimination half-life agents (lorazepam, alprazolam), compared with long-elimination half-life agents (diazepam, chlordiazepoxide) (Ciraulo et al. 2004). In 2001, alprazolam was the most widely prescribed benzodiazepine (Ciraulo et al. 2004), and it also was the most widely prescribed psychiatric medication in that year for mood and anxiety disorders (Stahl 2002). 

Clinical experience suggests that alprazolam can be particularly difficult to taper when lower doses are reached (e.g., tapering from 1 to 0 mg) (Ciraulo et al. 1990). One possible explanation for this is suggested by data from an animal model showing that alprazolam at doses of 0.02—0.05 mg/kg increases benzodiazepine receptor number above baseline (Miller et al. 1987). When difficulty is encountered in tapering the last 1—2 mg of alprazolam, the rate of dose reduction can be decreased to 0.25 mg/week, and/or adjunctive medication may... 

Other medication strategies have been shown to be of benefit in assisting alprazolam tapering. Clonazepam can be substituted gradually over the course of a week at an alprazolam-to-clonazepam equivalency ratio of 2 1 (Herman et al. 1987), and the clonazepam may be tapered as described earlier in this... 

In two studies in which benzodia2epines were gradually tapered, concurrent cognitive-behavioral therapy (CBT) did not increase the proportion of patients who were able to successfully discontinue their use of these agents (Oude Voshaar et al. 2003 Vorma et al. 2003). On the other hand, other studies of patients with panic disorder found that CBT facilitated the discontinuation of benzodiazepine use (Otto et al. 1993). Similarly, CBT may be superior to supportive medical management in preventing the reoccurrence of panic attacks in panic disorder patients in whom alprazolam has been tapered (Bruce etal. 1999). 

Bruce TJ, Spiegel DA, Hegel MT Cognitive-behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation a longterm follow-up of the Peoria and Dartmouth studies. J Consult Clin Psychol 67 151-156, 1999... 

Ciraulo DA, Nace EP Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Greenblatt DJ, et al Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men. J Clin Psychiatry 49 333—337, 1988a... 

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... 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

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