Alprazolam (Xanax)
Alprazolam
Alprazolam Intensol™ | Niravam™ | Xanax XR® | Xanax®
Classification:
Psychotropic Agents
Anxiolytics, Sedatives, and Hypnotics
Benzodiazepines
NOTE: Alprazolam is a schedule C-IV controlled substance.
Description: Alprazolam is an oral benzodiazepine used for the treatment of anxiety disorders including panic disorder with or without agoraphobia and generalized anxiety disorder. It is also used for the short term management of nonspecific anxiety.
Benzodiazepines may be used as sedatives, however, treatment options with less addiction potential should be considered prior to initiation of a benzodiazepine for this purpose. Alprazolam is often preferable to other benzodiazepines, such as chlordiazepoxide, clorazepate, and flurazepam because alprazolam has a shorter half-life and metabolites with minimal activity. However, alprazolam has a relatively high potential for abuse and if discontinuation becomes necessary, tapering of the drug may take weeks to months. Therefore, other short-acting, high-potency benzodiazepines without active metabolites such as lorazepam and oxazepam are preferred in most instances. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Therefore, it should be used cautiously, if at all, with significant inhibitors of this metabolic pathway. Alprazolam was approved by the FDA in 1981 and became available as a generic in 1993. The extended-release formulation of alprazolam (Xanax® XR) for treatment of panic disorder was granted approval by the FDA in January 2003. In general, the precautions, side effects, and drug interactions are similar between the immediate-release and extended-release formulations of alprazolam. On January 21, 2005, an orally disintegrating formulation of alprazolam (Niravam™) was approved by the FDA for use in generalized anxiety disorder and panic disorder.
Mechanism of Action: Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, and anticonvulsant activity. Recent evidence indicates that benzodiazepines exert their effects through enhancement of the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex. GABA is an inhibitory neurotransmitter that exerts its effects at specific receptor subtypes designated GABA-A and GABA-B. GABA-A is the primary receptor subtype in the CNS and is thought to be involved in the actions of anxiolytics and sedatives.
Specific benzodiazepine receptor subtypes are thought to be coupled to GABA-A receptors. Three types of BNZ receptors are located in the CNS and other tissues; the BNZ-1 receptors are located in the cerebellum and cerebral cortex, the BNZ-2 receptors in the cerebral cortex and spinal cord, and the BNZ-3 receptors in peripheral tissues. Activation of the BNZ-1 receptor is thought to mediate sleep while the BNZ-2 receptor affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. Benzodiazepines bind nonspecifically to BNZ-1 and BNZ-2 which ultimately enhances the effects of GABA. Unlike barbiturates which augment GABA responses by increasing the length of time that chloride channels are open, benzodiazepines enhance the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
 Alprazolam Tablet (Tab 2 mg)
Benzodiazepines alleviate insomnia by decreasing the latency to sleep and increasing sleep continuity and total sleep time through their effects on GABA. Preliminary evidence suggests that alprazolam decreases cerebral blood flow and plasma epinephrine concentrations.
Pharmacokinetics: Alprazolam is administered orally and is rapidly absorbed following administration. Peak plasma concentrations are attained within 1 - 2 hours of administration of the immediate-release tablets. The onset of action usually occurs within 15 - 30 minutes. The drug is widely distributed and is 90% plasma protein-bound, primarily to serum albumin. Alprazolam may cross the placenta and distribute into breast milk (alprazolam-xanax-contraindications-precautions/">see Contraindications). The half-life is 11.2 hours (range 6.3 - 26.9 hours). Alprazolam undergoes oxidative metabolism in the liver through CYP3A4, producing metabolites with little or no activity. The alpha-hydroxy-alprazolam metabolite is approximately one half as potent as the parent compound while the benzophenone derivative is inactive. Both metabolites are excreted primarily in the urine. The pharmacokinetics of alprazolam extended-release tablets are similar to the immediate-release tablets, except that the extended-release tablets have a slower rate of absorption and yield a constant concentration maintained between 5 and 11 hours after dosing. Although elevations up to 25% in the Cmax have been observed when extended-release tablets were given following a high-fat meal, the AUC and T1/2 were not affected by consumption of food. Additionally, alprazolam extended-release given at night (vs. the morning) results in a 30% higher Cmax and a reduction in Tmax by 1 hour. The rate of metabolism of alprazolam extended-release is not effected by the slower rate of absorption. The half-life of alprazolam extended-release ranges from roughly 11 to 16 hours.
- Special Populations: The mean half-life of immediate-release alprazolam is prolonged to 16.3 hours in the elderly compared to 11.2 hours in healthy subjects. In those with alcoholic liver disease, the half-life has ranged from 5.8 to 65.3 hours. In one group of obese patients, the mean half-life was 21.8 hours (range 9.9 - 40.4 hours). Patients with renal impairment should be carefully monitored during prolonged treatment with benzodiazepines to avoid the adverse reactions that may occur from drug accumulation. Alprazolam concentrations may be reduced by up to 50% in smokers vs. non-smokers. Pharmacokinetic studies have not been performed in special populations utilizing the extended-release formulation.
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[ Revised 7/19/2007 1:11:00 PM ]
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