Alprazolam is a triazolo analog of the 1,4 benzodiazepine class of central nervous system-active compounds. The chemical name is 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo benzodiazepine. It is a white, crystalline powder, which is soluble in methanol or ethanol, but is not appreciably soluble in water at physiological pH. It is used for the management of anxiety disorder or for short-term relief of symptoms of anxiety. Anxiety associated with depression is responsive to alprazolam. It is also used in the treatment of panic disorder, with or without agoraphobia. It was invented by using valium as a starting point, and removing all of the unnecessary pieces.

Mechanism

While the exact mechanism is not fully understood, CNS agents of the 1,4 benzodiazepine class are believed to operate by binding at stereo specific receptors at several sites within the CNS. However, all benzodiazepines cause dose-related CNS depression varying from "mild impairment of task performance" to hypnosis.

Dosage and Pharmacology

Alprazolam is most commonly prescribed in dosages ranging from 0.75 to 4.0mg per day. According to trials by Pharmacia & Upjohn, over a dose range of 0.5 to 3.0mg of alprazolam, peak levels in plasma of 8.0 to 37 ng/mL were observed. The mean plasma elimination half-life of alprazolam has been found to be about 11.2 hours (6.3 to 26.9 hours overall) in healthy adults.

Contraindications

Besides the usual warnings about patients who have a known sensitivity to this particular drug or to others in the same family (benzodiazepines), alprazolam is contraindicated in patients with acute narrow angle glaucoma. It is also not to be used with ketoconazole or itraconazole, as these medications interfere with the oxidization metabolism mediated by cytochrome P450 3A (CYP 3A).

Warnings and Precautions

Alprazolam is highly addictive. Discontinuing its use puts one at risk for seizures, and other negative physiological (and psychological) effects. The most common negative effects include insomnia, light-headedness, abnormal involuntary movement, headache, anxiety, fatigue, nausea (sometimes accompanied by vomiting), diarrhea, and sweating. The actual risk of seizure seems to be greatest between 24 and 72 hours after discontinuation. In two controlled trials of six to eight weeks in duration, as many as 29 percent of patients were unable to completely discontinue their use of alprazolam.

Episodes of both hypomania and mania have been reported in association with the use of alprazolam in patients with depression.

Like nearly any drug, alprazolam is not recommended for use during pregnancy, or while nursing. As it is a depressant, it makes operating heavy machinery (including automobiles) somewhat risky, at least until one is familiar with one's reaction to the drug. It is not recommended that it be mixed with alcohol, a common caution with benzodiazepines. In addition, any benzodiazepine will have an additive CNS-depressant effect when combined with other psychotropic medications, anticonvulsants, antihistaminics, ethanol, or other drugs which themselves produce CNS depression.

Notably, among other additive effects, the coadministration of oral contraceptives has been shown to increase the maximum plasma concentration of alprazolam by 18 percent, decrease clearance by 22 percent, and increase half-life by 29 percent.

Alprazolam has not been shown to be safe for those under the age of 18. In addition, it has been shown to have reduced clearance and a longer half-life in the elderly.

Overdosage

Overdose of alprazolam has been shown to cause somnolence, confusion, impaired coordination, diminished reflexes, and coma, as well as death. Fatality is made much more likely by the intake of alcohol.

The acute LD50 of alprazolam in rats is 331 to 2171 mg/kg. Other animal experiments have shown that direct intravenous introduction of doses over 195 mg/kg (approximately 975 times the maximum human dosage of 10mg per day) may cause cardiopulmonary collapse. Animals could be resuscitated with positive mechanical ventilation and the intravenous infusion of norepinephrine bitartate. The studies suggest that forced diuresis or hemodialysis are of little use in treating overdosage.

In the case of an alprazolam overdose, general supportive measures should be taken, along with immediate gastric lavage. Flumenazil is a specific benzodiazepine receptor antagonist and is indicated for partial or complete reversal of the sedative effects of benzodiazepines, though it is not to be considered a complete course for the treatment of overdosage of benzodiazepines, and carries a risk of seizure.


References:

PDR Edition 55 - 2001, pp.2650-2654

See also: This is a prescription drug used to treat anxiety. It is a central nervous system depressant, and can therefore have a negative impact on coordination and mental alertness. Side effects typically include drowsiness and/or mood changes.


From the BioTech Dictionary at http://biotech.icmb.utexas.edu/. For further information see the BioTech homenode.

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