| Item |
Information |
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Drug Groups
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illicit; approved; investigational |
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Description
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A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders. (From AMA Drug Evaluations Annual, 1994, p238) |
| Indication |
For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia. |
| Pharmacology |
Alprazolam, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking. |
| Toxicity |
Oral, mouse: LD50=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time. |
| Affected Organisms |
| • |
Humans and other mammals |
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| Biotransformation |
Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides. |
| Absorption |
Readily absorbed from the gastrointestinal tract. Bioavailability is 80-90%. |
| Half Life |
6.3-26.9 hours |
| Protein Binding |
80% (mainly to albumin) |
| Elimination |
Alprazolam and its metabolites are excreted primarily in the urine. |
| Clearance |
* 2.13 +/- 0.54 mL/min/kg [CYP3A inducers]
* 0.90 +/- 0.21 mL/min/kg [without CYP3A inducers] |
| References |
| • |
Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA: Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. J Clin Psychiatry. 1990 May;51(5):206-9.
[Pubmed]
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Wolf B, Griffiths RR: Physical dependence on benzodiazepines: differences within the class. Drug Alcohol Depend. 1991 Dec 31;29(2):153-6.
[Pubmed]
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Haque W, Watson DJ, Bryant SG: Death following suspected alprazolam withdrawal seizures: a case report. Tex Med. 1990 Jan;86(1):44-7.
[Pubmed]
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Hori A: Pharmacotherapy for personality disorders. Psychiatry Clin Neurosci. 1998 Feb;52(1):13-9.
[Pubmed]
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Garcia-Algar O, Lopez-Vilchez MA, Martin I, Mur A, Pellegrini M, Pacifici R, Rossi S, Pichini S: Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis. Clin Toxicol (Phila). 2007;45(3):295-8.
[Pubmed]
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