Alprazolam chemical structurealprazolam 2mg tablet bottlealprazolam 2mg tablets
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Alprazolam

Alprazolam is a drug which is a benzodiazepine derivative. It is classified as short-acting, and is used to treat anxiety disorders and insomnia. more...

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Pharmacology

Alprazolam is a triazolobenzodiazepine, that is, a benzodiazepine with a triazolo-ring attached to its structure. Alprazolam binds to the GABAA subtype of the GABA receptor, increasing inhibitory effects of GABA within the central nervous system. The binding site for benzodiazepines is distinct from the binding site for GABA on the GABA receptor.

Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.

Pharmacokinetics

The mechanism of action is not fully understood; However, Alprazolam is readily absorbed from the gastrointestinal tract. The peak plasma concentration is achieved in 1-2 hours. Most of the drug is bound to plasma protein, mainly albumin. Alprazolam is hydroxylated in the liver to α-hydroxyalprazolam, which is also pharmacologically active. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form.

Indications

The main medical uses for alprazolam include:

  • Treatment of panic disorder, with or without agoraphobia.
    Alprazolam is very effective in preventing panic attacks. However, despite its efficacy, many psychiatrists are reluctant to use alprazolam for this condition because of the possibility of dependence and interdose anxiety due to its short-acting nature. An extended-release formulation of alprazolam known as Xanax XR® was introduced in 2001 and is often preferred.
  • Treatment of panic attacks.
    Alprazolam is taken as needed (PRN); 4 to 6 doses per month are the acceptable limit. If dependence seems to develop and/or the limit is exceeded, therapy may be reconsidered and/or discontinued.
  • Long-term treatment of severe generalized anxiety disorders.
    Alprazolam may be used for long-term treatment of anxiety if other therapies either do not work or are contraindicated. Duration of therapy in this case is often four months or longer. The decision to use alprazolam for this purpose must be carefully made by a specialized psychiatrist, taking into account the individual's suffering, quality of life, loss of social performance and risk of dependence.
  • Adjunctive treatment of depression.
    Alprazolam is sometimes used together with SSRIs such as paroxetine, sertraline, or fluoxetine to alleviate initial SSRI-induced anxiety while waiting for the antidepressant to begin working. However, clinical experience has shown that SSRIs may actually provoke panic attacks in otherwise healthy individuals, and cause sexual dysfunction. In these cases, a tricyclic antidepressant may be used instead. Buspirone may also be useful in conjunction with alprazolam in cases of generalized anxiety disorder.
  • Other uses.
    Alprazolam may be used by specialists to treat severe cases of Borderline Personality Disorder. Some studies have shown positive results.

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AAN releases recommendations for managing essential tremor
From American Family Physician, 11/1/05 by Amber Huntzinger

The Quality Standards Subcommittee of the American Academy of Neurology (AAN) has released evidence-based recommendations for the initiation of pharmacologic and surgical therapies for patients with essential tremor. The recommendations are based on a systematic literature review and were rated for strength of evidence. The full report was published in the June 28, 2005, issue of Neurology and can be found online at http://www. neurology.org/cgi/content/full/64/12/2008.

Essential tremor is defined as the presence of postural and kinetic tremor. Classic essential tremor most commonly affects the upper limbs, but it also can affect a head, lower limbs, voice, tongue, face, and trunk. Although essential tremor does not reduce life expectancy, and symptoms are limited to tremors, the condition may cause substantial physical and psychosocial disability (e.g., difficulty with writing, drinking, eating, dressing, speaking, and other fine motor skills). Propranolol (Inderal) is the only drug approved by the U.S. Food and Drug Administration for the management of essential tremor. However, an estimated 30 percent of patients will not respond to this medication. Other drugs may be used, and surgical intervention is an invasive alternative to pharmacologic therapy.

Recommendations

PHARMACOLOGIC THERAPY

Table 1 summarizes the evidence for the pharmacologic management of essential tremor.

Level A. Propranolol was effective in managing limb tremor related to essential tremor. The results of treatment with once-daily, long-acting propranolol (Inderal LA) were similar to those of standard propranolol in managing limb tremors. Physicians might consider the use of propranolol, long-acting propranolol, or primidone (Mysoline) to manage limb tremor in patients with essential tremor, depending on concurrent medical conditions and potential side effects. Primidone and propranolol were equally effective for initial treatment of patients with limb tremor.

Trazodone (Desyrel) did not significantly affect postural or kinetic tremor and is not recommended for managing limb tremor.

Level B. Alprazolam (Xanax), atenolol (Tenormin), gabapentin (Neurontin) mono-therapy, sotalol (Betapace), and topiramate (Topamax) may reduce limb tremor associated with essential tremor. Atenolol, gabap-patient's entin monotherapy, sotalol, and topiramate may be used for limb tremor, although data are limited. Alprazolam should be used with caution because of the potential for abuse. Propranolol should be considered for the management of head tremor.

Acetazolamide (Diamox), isoniazid (INH), and pindolol (Visken) probably do not reduce limb tremor and are not recommended for managing essential tremor.

Level C. Nadolol (Corgard) and nimodipine (Nimotop) may be considered to manage limb tremor associated with essential tremor, but clonazepam (Klonopin) should be used with caution because of its potential for abuse and withdrawal symptoms. Clozapine (Clozaril) is recommended only for refractory cases of essential tremor because of the risk of agranulocytosis.

Methazolamide (Neptazane), mirtazapine (Remeron), nifedipine (Procardia), and verapamil (Calan) probably do not reduce limb tremor and are not recommended for managing essential tremor.

SURGICAL THERAPY

Table 2 summarizes the evidence for the surgical management of essential tremor. Surgical intervention should be considered only for patients who do not respond to pharmacologic therapy.

Level C. Sufficient evidence was available only on the effectiveness of chronic thalamic deep brain stimulation (DBS) and thalamotomy for managing essential tremor. Unilateral thalamotomy may be used to manage limb tremor, but bilateral thalamotomy is not recommended because of adverse effects. Thalamic DBS may be used to treat patients with limb tremor, but insufficient evidence exists to make a recommendation regarding its effectiveness in managing head and voice tremor. Although DBS has fewer adverse effects, physicians should choose between DBS and thalamotomy based on the patient's intraoperative complications compared with the practicality of the procedures.

Level U. gamma knife surgery, chronic thalamic DBS (head), chronic thalamic DBS (voice), and unilateral versus bilateral DBS (hand) should be considered unproven therapies at this time.

Conclusion

The committee concludes that research on the management of essential tremor is limited, and additional prospective, double-blind, placebo-controlled trials are needed to better determine the effectiveness and side effects of pharmacologic and surgical therapy for essential tremor.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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