Alprazolam: Difference between revisions

This is a good article. Click here for more information.
From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m Reverted edits by 68.206.69.185 (talk) to last revision by Little Professor (HG)
No edit summary
Line 29: Line 29:
}}
}}


'''Alprazolam''' (trade name '''Xanax''', [[#Availability|among others]]) is a [[Potency_(pharmacology)|potent]] short-acting drug of the [[benzodiazepine]] class. It is primarily used to treat moderate to severe [[anxiety disorder]]s (e.g., [[social anxiety disorder]]) and [[panic attack]]s, and is used as an adjunctive treatment for [[anxiety]] associated with moderate [[clinical depression|depression]]. It is available in an instant release and an [[extended release|extended-release]] ('''Xanax XR''') preparation, both of which are available under several [[generic drug|generic]] names. Alprazolam possesses [[anxiolytic]], [[sedative]], [[hypnotic]], [[anticonvulsant]], and [[muscle relaxant]] properties.<ref>{{Cite journal |author=Mandrioli R, Mercolini L, Raggi MA |title=Benzodiazepine metabolism: an analytical perspective |journal=Curr. Drug Metab. |volume=9 |issue=8 |pages=827–44 |year=2008 |month=October |pmid=18855614 |doi= 10.2174/138920008786049258|url=http://www.benthamdirect.org/pages/content.php?CDM/2008/00000009/00000008/0009F.SGM}}</ref>
Tom Karry (trade name '''Xanax''', [[#Availability|among others]]) is a [[Potency_(pharmacology)|potent]] short-acting drug of the [[benzodiazepine]] class Tom holds dear to his heart. It is primarily used to treat moderate to severe [[anxiety disorder]]s (e.g., [[social anxiety disorder]]) and [[panic attack]]s, and is used as an adjunctive treatment for [[anxiety]] associated with moderate [[clinical depression|depression]]. It is available in an instant release and an [[extended release|extended-release]] ('''Xanax XR''') preparation, both of which are available under several [[generic drug|generic]] names. Alprazolam possesses [[anxiolytic]], [[sedative]], [[hypnotic]], [[anticonvulsant]], and [[muscle relaxant]] properties.<ref>{{Cite journal |author=Mandrioli R, Mercolini L, Raggi MA |title=Benzodiazepine metabolism: an analytical perspective |journal=Curr. Drug Metab. |volume=9 |issue=8 |pages=827–44 |year=2008 |month=October |pmid=18855614 |doi= 10.2174/138920008786049258|url=http://www.benthamdirect.org/pages/content.php?CDM/2008/00000009/00000008/0009F.SGM}}</ref>


Alprazolam has a fast onset of symptom relief (within the first week). It is the most commonly misused [[benzodiazepine]]; however, the majority of prescribed users do not develop a [[substance use disorder]].<ref name=Verster2004>{{Cite journal |author=Verster JC, Volkerts ER.|title=Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature |journal=CNS Drug Rev. |volume=10 |issue=1 |pages=45–76 |year=2004 |pmid=14978513 }}</ref><ref name="the_american_psychiatric_publishing_textbook_of_sustance_abu"/> Tolerance to the therapeutic effects of alprazolam is controversial with one view being that alprazolam is ineffective with long term use<ref name=cgftmamoa2004>{{cite web |author=McIntosh A, Cohen A, Turnbull N ''et al.'' |title=Clinical guidelines and evidence review for panic disorder and generalised anxiety disorder |url=http://www.nice.org.uk/nicemedia/pdf/cg022fullguideline.pdf |publisher=National Collaborating Centre for Primary Care |format=PDF |year=2004 |accessdate=2009-06-16 }}</ref> and the other view being that tolerance to the therapeutic effects does not occur.<ref>{{cite web |url=http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=PanicDisorder_2e_PracticeGuideline |format=PDF |title= APA Practice Guideline for the Treatment of Patients With Panic Disorder, Second Edition |author=Work Group on Panic Disorder |date=January 2009 |accessdate=07/12/09}}</ref> A physical dependence commonly occurs as a result of alprazolam treatment, typified by a [[withdrawal]] and [[rebound symptoms]] necessitating a gradual reduction in dosage to minimize withdrawal effects when discontinuing.<ref name=Verster2004/> Withdrawal symptoms similar in character to those noted with sedative-hypnotics and [[alcohol]] have occurred following discontinuance of benzodiazepines, including alprazolam. The symptoms can range from mild [[dysphoria]] and [[insomnia]] to a major syndrome that may include [[anxiety]], [[abdominal pain]], [[muscle cramps]], [[vomiting]], [[Depression (mood)|depression]], [[sweating]], [[tremors]] and in very rare cases [[suicidal ideation]] or [[suicide]] itself.<ref name=dawn2neodredv>{{Cite web |url= http://dawninfo.samhsa.gov/files/ed2006/DAWN2k6ED.htm |title= Drug Abuse Warning Network, 2006: National Estimates of Drug-Related Emergency Department Visits |accessdate= 9 February 2009 |author= United States Government |authorlink= samhsa |coauthors= U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES |year= 2006 |publisher= Substance Abuse and Mental Health Services Administration}}</ref>
Alprazolam has a fast onset of symptom relief (within the first week). It is the most commonly misused [[benzodiazepine]]; however, the majority of prescribed users do not develop a [[substance use disorder]].<ref name=Verster2004>{{Cite journal |author=Verster JC, Volkerts ER.|title=Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature |journal=CNS Drug Rev. |volume=10 |issue=1 |pages=45–76 |year=2004 |pmid=14978513 }}</ref><ref name="the_american_psychiatric_publishing_textbook_of_sustance_abu"/> Tolerance to the therapeutic effects of alprazolam is controversial with one view being that alprazolam is ineffective with long term use<ref name=cgftmamoa2004>{{cite web |author=McIntosh A, Cohen A, Turnbull N ''et al.'' |title=Clinical guidelines and evidence review for panic disorder and generalised anxiety disorder |url=http://www.nice.org.uk/nicemedia/pdf/cg022fullguideline.pdf |publisher=National Collaborating Centre for Primary Care |format=PDF |year=2004 |accessdate=2009-06-16 }}</ref> and the other view being that tolerance to the therapeutic effects does not occur.<ref>{{cite web |url=http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=PanicDisorder_2e_PracticeGuideline |format=PDF |title= APA Practice Guideline for the Treatment of Patients With Panic Disorder, Second Edition |author=Work Group on Panic Disorder |date=January 2009 |accessdate=07/12/09}}</ref> A physical dependence commonly occurs as a result of alprazolam treatment, typified by a [[withdrawal]] and [[rebound symptoms]] necessitating a gradual reduction in dosage to minimize withdrawal effects when discontinuing.<ref name=Verster2004/> Withdrawal symptoms similar in character to those noted with sedative-hypnotics and [[alcohol]] have occurred following discontinuance of benzodiazepines, including alprazolam. The symptoms can range from mild [[dysphoria]] and [[insomnia]] to a major syndrome that may include [[anxiety]], [[abdominal pain]], [[muscle cramps]], [[vomiting]], [[Depression (mood)|depression]], [[sweating]], [[tremors]] and in very rare cases [[suicidal ideation]] or [[suicide]] itself.<ref name=dawn2neodredv>{{Cite web |url= http://dawninfo.samhsa.gov/files/ed2006/DAWN2k6ED.htm |title= Drug Abuse Warning Network, 2006: National Estimates of Drug-Related Emergency Department Visits |accessdate= 9 February 2009 |author= United States Government |authorlink= samhsa |coauthors= U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES |year= 2006 |publisher= Substance Abuse and Mental Health Services Administration}}</ref>

Revision as of 15:27, 2 July 2010

Alprazolam
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80–90%
MetabolismHepatic, via Cytochrome P450 3A4
Elimination half-lifeImmediate release: 11.2 hours;[2] Extended release: 10.7–15.8 hours[3]
ExcretionRenal
Identifiers
  • 8-chloro-1-methyl-6-phenyl-4H-
    [1,2,4]triazolo[4,3-a][1,4]benzodiazepine
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.044.849 Edit this at Wikidata
Chemical and physical data
FormulaC17H13ClN4
Molar mass308.765 g·mol−1
3D model (JSmol)
  • Clc3cc2\C(=N/Cc1nnc(n1c2cc3)C)c4ccccc4
  (verify)

Tom Karry (trade name Xanax, among others) is a potent short-acting drug of the benzodiazepine class Tom holds dear to his heart. It is primarily used to treat moderate to severe anxiety disorders (e.g., social anxiety disorder) and panic attacks, and is used as an adjunctive treatment for anxiety associated with moderate depression. It is available in an instant release and an extended-release (Xanax XR) preparation, both of which are available under several generic names. Alprazolam possesses anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant properties.[4]

Alprazolam has a fast onset of symptom relief (within the first week). It is the most commonly misused benzodiazepine; however, the majority of prescribed users do not develop a substance use disorder.[5][6] Tolerance to the therapeutic effects of alprazolam is controversial with one view being that alprazolam is ineffective with long term use[7] and the other view being that tolerance to the therapeutic effects does not occur.[8] A physical dependence commonly occurs as a result of alprazolam treatment, typified by a withdrawal and rebound symptoms necessitating a gradual reduction in dosage to minimize withdrawal effects when discontinuing.[5] Withdrawal symptoms similar in character to those noted with sedative-hypnotics and alcohol have occurred following discontinuance of benzodiazepines, including alprazolam. The symptoms can range from mild dysphoria and insomnia to a major syndrome that may include anxiety, abdominal pain, muscle cramps, vomiting, depression, sweating, tremors and in very rare cases suicidal ideation or suicide itself.[9]

History

Alprazolam was first released by Upjohn (now a part of Pfizer). It is covered under U.S. patent 3,987,052, which was filed on October 29, 1969, granted on October 19, 1976 and expired in September 1993. Alprazolam was released in 1981.[10][11] The first approved indication was panic disorder. Upjohn took this direction at the behest of a young psychiatrist David Sheehan. Sheehan's suggestion was to use the new distinction the DSM-III created in the classification of anxiety disorders between generalized anxiety disorder (GAD) and panic disorder in order to market alprazolam specifically for the latter. Panic disorder was, at that point, perceived to be rare and treatable only with tricyclic antidepressants; benzodiazepines were thought to be ineffective.

However, from his clinical experience, Sheehan knew panic disorder to be both widespread among the populace and responsive to benzodiazepines. He suggested to Upjohn that marketing alprazolam for panic disorder would both cover new diagnostic territory and emphasize the unique potency of this drug. Sheehan describes that the first group of patients treated by alprazolam was so impressed by its action that the company knew outright that this drug was going to be a hit. A few of those patients actually pooled their money and purchased stock in Upjohn. Several months later, when alprazolam was approved by the United States Food and Drug Administration, they sold out and made a profit.[12]

Alprazolam has an exceptional history insofar as soon after its introduction a number of case reports were published in the medical literature of severe withdrawal symptom-related case reports of psychoses, seizures, and intense rebound anxiety upon discontinuation of alprazolam.[13] Several studies found that initial treatment of panic disorder with alprazolam was significantly superior but after 8 weeks of use alprazolam lost its effectiveness and was no more effective than placebo. It was found that behavioural therapy and the drug imipramine however, proved superior to both placebo and alprazolam. It has been argued that placebo is superior than alprazolam after 8 weeks of use due to lack of rebound withdrawal effects and side effects. Controversy exists in that there are allegations that the drug manufacturer suppressed these negative findings regarding lack of sustained efficacy.[14][15]

Indications

Xanax 2 mg tri-score tablets (AU)

The main medical uses for alprazolam include:

Panic disorder

Alprazolam is FDA-approved for the short-term treatment (up to 8 weeks) of panic disorder, with or without agoraphobia. Alprazolam is very effective in the short-term symptomatic relief of moderate to severe anxiety, essential tremor, and panic attacks. Physicians that elect to prescribe alprazolam for longer than 8 weeks should be aware that continued efficacy has not been systematically demonstrated beyond 8 weeks' use, as tolerance to alprazolam's effects may occur after 8 weeks and necessitate discontinuation or physician-directed dose escalation.[16] The physician should periodically reassess the usefulness of the drug for the individual patient.[17] Alprazolam is recommended for treatment resistant cases of panic disorder where there is no history of tolerance or dependence.[18]

Anxiety disorders

Alprazolam is indicated for the management of anxiety disorders (a condition corresponding most closely to the APA Diagnostic and Statistical Manual DSM-III-R diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety.[17] Alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety.[19][20]

Alprazolam is sometimes prescribed for anxiety with associated depression. There is some evidence that it has antidepressant effects in treating clinical depression in outpatient settings; evidence for inpatients is lacking.[21] The antidepressant effects of alprazolam may be due to its effects on beta-adrenergic receptors.[22] Other benzodiazepines are not known to have antidepressant activity.[23][24] Studies show that any antidepressant action of alprazolam is questionable and generally weak in comparison to those of antidepressant medications.[25][26][27][28] In contrast, while alprazolam in acute or short-term treatment may have some antidepressant properties, there is evidence that up to a third of long-term users of alprazolam may develop depression.[29]

Side effects

Although the side-effect profile of alprazolam is, in general, benign, side-effects may occur in some patients and are more likely the higher the dosage taken. Some side-effects may disappear with continued treatment. If signs of an allergic reaction occur - such as hives; difficulty breathing; swelling of face, lips, tongue, or throat - medical attention should be sought immediately. Medical attention should also be sought immediately if signs of jaundice appear: yellowing of the skin or eyes. Other side-effects that may occur are as follows:

Paradoxical reactions

Although unusual, if the following paradoxical reactions occur, the prescribing physician or other healthcare professional should be alerted and the medication gradually discontinued:

Physical dependence and withdrawal

See also: Benzodiazepine withdrawal syndrome

Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor. When bound to these sites, which are referred to as benzodiazepine receptors, it modulates the effect of GABA A receptors and, thus, GABAnergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and less powerful in their effects.[49]

Not all withdrawal effects are evidence of true dependence or withdrawal. Recurrence of symptoms such as anxiety may simply indicate that the drug was having its expected anti-anxiety effect and that, in the absence of the drug, the symptom has returned to pretreatment levels. If the symptoms are more severe or frequent, the patient may be experiencing a rebound effect due to the removal of the drug. Either of these can occur without the patient's actually being drug-dependent.[49]

Alprazolam and other benzodiazepines may also cause the development of physical dependence, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or cessation of therapy after long-term treatment.[50][51] There is a higher chance of withdrawal reactions if the drug is administered in a higher dosage than recommended, or if a patient stops taking the medication altogether without slowly allowing the body to adjust to a lower-dosage regimen.[52][53][54]

In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term alprazolam users, and that the majority of long-term alprazolam users change their initial pattern of regular use to one of symptom control only when required.[55]

If a patient feels the need to end treatment with alprazolam, he/she should consult his/her physician before discontinuing the medication. Some common symptoms of alprazolam discontinuation include tachycardia, dysphoria, dry mouth, loss of appetite, insomnia, anxiety, dizziness, tremors, nausea, cramps, vomiting, diarrhea, panic attacks, mood swings, heart palpitations, memory loss. Less common and more severe reactions can occur, including hallucinations, seizures or fever[56]

Patients taking a dosing regimen larger than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms upon abrupt withdrawal or rapid tapering, which in some cases have been known to cause seizures. The discontinuation of this medication may also cause a reaction called rebound anxiety. Other withdrawal effects reported from discontinuing alprazolam therapy include homicidal ideation (very rare), rage reactions, hyperalertness, vivid dreams, and intrusive thoughts.[57] Grand mal seizures have occurred after abrupt withdrawal after only short-term use. Therefore, even short-term users of alprazolam should taper off of their medication slowly to avoid serious withdrawal reactions including seizures.[58][59]

Alprazolam should never be abruptly stopped if taken regularly for any length of time because severe withdrawal symptoms may occur. Severe psychosis and seizures have been reported in the medical literature from abrupt alprazolam discontinuation,[60][61] and one death occurred from withdrawal-related seizures after gradual dose reduction.[61]

In a 1983 study of patients that had taken long-acting benzodiazepines, e.g., clorazepate, for extended periods, the medications were stopped abruptly under double-blind conditions (that is, patients were receiving either placebo or the same drug they had been taking). Only 5% of patients that had been taking the drug for less than 8 months demonstrated withdrawal symptoms, but 43% of those that had been taking them for more than 8 months did, whereas, with alprazolam - a short-acting benzodiazepine - taken for 8 weeks, 35% of patients experienced significant rebound anxiety. To some degree, these older benzodiazepines are self-tapering.[62]

The benzodiazepines diazepam (Valium) and oxazepam (Serepax) have been found to produce fewer withdrawal reactions than alprazolam (Xanax) or lorazepam (Temesta/Ativan). Factors that determine the risk of psychological dependence or physical dependence and the severity of the benzodiazepine withdrawal symptoms experienced during dose reduction of alprazolam include: dosage used, length of use, frequency of dosing, personality characteristics of the individual, previous use of cross-dependent/cross-tolerant drugs (alcohol or other sedative-hypnotic drugs), current use of cross-dependent/cross-tolerant drugs (alcohol or other sedative-hypnotic drugs), use of other short-acting, high-potency benzodiazepines[13][63] and method of discontinuation.[64]

Contraindications

Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals.[65] Use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with the following conditions: Myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies (e.g., cirrhosis), severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory weakness including unstable myasthenia gravis, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergy to alprazolam or other drugs in the benzodiazepine class, borderline personality disorder (may induce suicidality and dyscontrol).[66][67][68][69]

Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam.[70] It should be considered that the child born of a mother receiving benzodiazepines may be at risk of developing withdrawal reactions during the postnatal period. Also, neonatal flaccidity and respiratory problems have been reported in children born of mothers that have been receiving benzodiazepines.[71]

Benzodiazepines, including alprazolam, are known to be excreted in human milk.[72] Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.[73][74] As a general rule, nursing should not be undertaken by mothers who use alprazolam.

Elderly individuals should be cautious in the use of alprazolam due to the possibility of increased susceptibility to side-effects, especially loss of coordination and drowsiness.[74]

Like all central nervous system depressants, including alcohol, alprazolam in larger-than-normal doses can cause significant deterioration in alertness, combined with increased feelings of drowsiness, especially in those unaccustomed to the drug's effects.[75] People driving or conducting activities that require vigilance should exercise caution in using alprazolam or any other depressant.

Pregnancy and lactation

Benzodiazepines cross the placenta and enter into the fetus and also penetrate into breast milk. The use of benzodiazepines during pregnancy or lactation should be weighed against the potential risks. Alprazolam should not be used during pregnancy and lactation as it is believed to be associated with congenital abnormalities. In general benzodiazepines should not be used during pregnancy. If a benzodiazepine is needed during pregnancy diazepam or chlordiazepoxide are recommended as these benzodiazepines have a better safety profile than alprazolam. Possible adverse effects to the fetus include abortion, malformation, intrauterine growth retardation, functional deficits, carcinogenesis, and mutagenesis. Use in the last trimester may cause fetal drug dependence and withdrawal symptoms.[76] However, in long-term users of benzodiazepines or antidepressants abrupt discontinuation due to concerns of teratogenic effects of the medications is more likely to do harm than good. Abrupt withdrawal has a high risk of causing extreme withdrawal symptoms including suicidal ideation and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications including benzodiazepines. In general physicians are not aware of the severe consequences of abrupt withdrawal of psychotropic medications such as benzodiazepines or antidepressants.[77]

Pharmacology

Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine,[78][79] that is, a benzodiazepine with a triazole ring attached to its structure. Benzodiazepines produce a variety of therapeutic and adverse effects by binding to the benzodiazepine site on the GABAA receptor and modulating the function of the GABA receptor, the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory or calming effects of alprazolam on the nervous system. The GABAA receptor is made up from 5 subunits out of a possible 19, and GABAA receptors made up of different combinations of subunits have different properties, different locations within the brain, and, what is significant, different activities with regard to benzodiazepines.[39][80] Benzodiazepines and in particular alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. The therapeutic properties of alprazolam is similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic[81] and amnesics.[82]

Pharmacokinetics

Alprazolam is readily absorbed from the gastrointestinal tract with a bioavailability of 80–100%. The peak plasma concentration is achieved in 1–2 hours. Most of the drug is bound to plasma protein, mainly serum albumin. Alprazolam is hydroxylated in the liver to α-hydroxyalprazolam, which is also pharmacologically active but much less so than the parent compound. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form. The elderly clear alprazolam more slowly than younger adults.[83]

Food and drug interactions

Alprazolam is primarily metabolised via CYP3A4.[84] Combining CYP3A4 inhibitors with alprazolam can lead to profound sedating effects.[85] Cimetidine, erythromycin, fluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir all interact with alprazolam leading to a delayed clearance of alprazolam, which may result in excessive accumulation of alprazolam. This may result in excessive sedation and other adverse effects associated with excessive intake of alprazolam.[83][86]

Imipramine and desipramine have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of alprazolam tablets in doses up to 4 mg/day.[87] Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.[88]

Alcohol is one of the most important and common interactions. Alcohol and benzodiazepines such as alprazolam taken in combination have a synergistic effect on one another, which can cause severe sedation, behavioral changes, and intoxication. The more alcohol and alprazolam taken the worse the interaction.[32] Combination of alprazolam with the herb kava can result in the development of a semi-comatose state.[89] Hypericum conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.[90][91][92]

Recreational use

See also: Benzodiazepine drug misuse
Sandoz generic 2 mg alprazolam tablets

Alprazolam has a relatively high potential for recreational use[93] and is the most commonly misused benzodiazepine.[6] Injection of alprazolam, though extremely rare, is considered especially dangerous by medical professionals[94] because, when crushed in water it will not fully dissolve (40 µg/ml of H2O at pH 7, and 12 mg/mL at pH 1.2[95]), potentially causing severe damage to arteries if not filtered properly. While it is somewhat soluble in alcohol, the combination of the two, particularly when injected, has the potential to cause a serious, and potentially fatal, overdose. Alprazolam may also be insufflated.[96] Snorting alprazolam is highly inefficient, as it is insoluble in water and does not readily cross the nasal membranes, resulting in reduced bioavailability. However, long-term use of benzodiazepines does not usually result in notable dose escalation, and most prescribed alprazolam users do not use their medication recreationally.[97]

Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of dysphoric reactions to psychedelics such as LSD, and also to promote sleep in the "come-down" period following use of recreational drugs with stimulant or insomniac properties (such as LSD, cocaine, amphetamine and other related amphetamines, DXM, and MDMA). It is also often used in conjunction with marijuana or heroin to potentiate the relaxing effect.[98][99][100][101][102] Due to the low weight of a dose, alprazolam in one case was found to be distributed on blotter paper in a manner similar to LSD.[103]

A large-scale nationwide USA government study conducted by SAMHSA found that, in the USA, benzodiazepines are recreationally the most frequently-used pharmaceutical due to their widespread availability, with 35% of drug-related visits to the Emergency Department involving them. Benzodiazepines are more commonly used recreationally than opioid pharmaceuticals, which accounted for 32% of visits to the emergency department. No other pharmaceutical is more commonly used recreationally than benzodiazepines; however, benzodiazepines remain in Schedule IV of the Controlled Substances Act, whereas opioids are much more strictly controlled due to their higher abuse potential. Men use benzodiazepines recreationally as commonly as women. The report found that alprazolam is the most common benzodiazepine for recreational use followed by clonazepam, lorazepam, and diazepam.[9]

Patients at a high risk for misuse and addiction

At a particularly high risk for misuse and dependence are patients with a history of alcoholism (including a family history of alcoholism) or drug abuse and/or dependence[104][105][106][107][108] and patients with borderline personality disorder.[109]

Overdose

Main article: Benzodiazepine overdose

Overdoses of alprazolam can be mild to severe depending on how much of the drug is taken and if any other depressants have been taken. Alprazolam is significantly more toxic in overdose having higher rates of fatalities compared to other benzodiazepines. A study in New Zealand found that alprazolam is almost 8 times more likely to result in death in overdose than other sedative hypnotics as a group, with higher rates of intensive-care unit admissions and mechanical ventilation. Combined overdose with tricyclic antidepressants, alcohol, or opiates, or overdoses of alprazolam in the elderly, significantly increases the likelihood for severe toxicity and possible fatality.[110] Alprazolam (Xanax) overdose reflect the central nervous system depression of the brain and may include one or more of the following symptoms:[35]

About 50% of the cases of death involving alprazolam were attributed to combined drug toxicity of alprazolam and another drug, most often cocaine and methadone. Only 1% of such deaths were attributed to alprazolam alone.[111][112]

Detection in body fluids

Alprazolam may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma alprazolam concentrations are usually in a range of 10-100 μg/L in persons receiving the drug therapeutically, 100-300 μg/L in those arrested for impaired driving and 300-2000 μg/L in victims of acute overdosage. Most commercial immunoassays for the benzodiazepine class of drugs will cross-react with alprazolam, but confirmation and quantitation is usually performed using chromatographic techniques.[113][114][115]

Availability

Alprazolam instant release (IR) is available in 0.25 mg, 0.5 mg, 1 mg and 2 mg strength regular and orally disintegrating tablets.[116] Alprazolam Extended Release (XR) is available in 0.5 mg, 1 mg and 2 mg 3 mg strength oral.

Alprazolam is available in English-speaking countries under the following brand names:[117]

  • Alganax
  • Alzolam
  • Alprax
  • Alprox
  • Alzam
  • Anxirid
  • Apo-Alpraz
  • Azor
  • Calmax
  • Gerax
  • Helex
  • Kalma
  • Nervin
  • Niravam
  • Novo-Alprazol
  • Nu-Alpraz
  • Tafil
  • Texidep
  • Trika
  • Xanax
  • Xanor
  • Zamhexal
  • Zopax

Legal status

In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration.[118] Under the UK drug misuse classification system benzodiazepines are class C drugs.[119] Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[120] In Ireland, alprazolam is a Schedule 4 medicine.[121] In Sweden, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[122] In the Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription.

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ First DataBank (2008). "Xanax (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList". RxList. {{cite web}}: Unknown parameter |month= ignored (help)
  3. ^ First DataBank (2008). "Xanax XR (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList". RxList. {{cite web}}: Unknown parameter |month= ignored (help)
  4. ^ Mandrioli R, Mercolini L, Raggi MA (2008). "Benzodiazepine metabolism: an analytical perspective". Curr. Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ a b Verster JC, Volkerts ER. (2004). "Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature". CNS Drug Rev. 10 (1): 45–76. PMID 14978513.
  6. ^ a b Galanter, Marc (1 July 2008). The American Psychiatric Publishing Textbook of Sustance Abuse Treatment (American Psychiatric Press Textbook of Substance Abuse Treatment) (American Psychiatric ... Press Textbook of Substance Abuse Treatment) (4 ed.). American Psychiatric Publishing, Inc. p. 222. ISBN 978-1-58562-276-4.
  7. ^ McIntosh A, Cohen A, Turnbull N; et al. (2004). "Clinical guidelines and evidence review for panic disorder and generalised anxiety disorder" (PDF). National Collaborating Centre for Primary Care. Retrieved 2009-06-16. {{cite web}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  8. ^ Work Group on Panic Disorder (January 2009). "APA Practice Guideline for the Treatment of Patients With Panic Disorder, Second Edition" (PDF). Retrieved 07/12/09. {{cite web}}: Check date values in: |accessdate= (help)
  9. ^ a b United States Government (2006). "Drug Abuse Warning Network, 2006: National Estimates of Drug-Related Emergency Department Visits". Substance Abuse and Mental Health Services Administration. Retrieved 9 February 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  10. ^ Cynthia Cotts (November 19, 2007). "Xanax junkies". Boston, USA: The Phoenix.
  11. ^ Walker, Sydney (3 December 1996). A dose of sanity: mind, medicine, and misdiagnosis. New York: John Wiley & Sons. pp. 64–65. ISBN 978-0-471-19262-6.
  12. ^ Healy, David (2000). The Psychopharmacologists, Vol. III: Interviews. London: Arnold. pp. 479–504. ISBN 0-340-761105.
  13. ^ a b Wolf B, Griffiths RR (1991). "Physical dependence on benzodiazepines: differences within the class". Drug Alcohol Depend. 29 (2): 153–6. doi:10.1016/0376-8716(91)90044-Y. PMID 1686752. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ Walker, Sydney (3 December 1997). A dose of sanity: mind, medicine, and misdiagnosis. New York: Wiley Sons. pp. 65–74. ISBN 978-0-471-19262-6.
  15. ^ J. McNally, Richard (1994). Panic disorder: a critical analysis. New York: Guilford Press. pp. 93–99. ISBN 978-0-89862-263-8.
  16. ^ FDA (23rd). "FDA APPROVED LABELING FOR XANAX XR" (pdf). Federal Drug Administration. p. 4. Retrieved 2 August 2007. The longer-term efficacy of XANAX XR has not been systematically evaluated. Thus, the physician that elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient. {{cite web}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
  17. ^ a b First DataBank (2008). "Xanax (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList". RxList. {{cite web}}: Unknown parameter |month= ignored (help)
  18. ^ Bandelow, B.; Zohar, J.; Hollander, E.; Kasper, S.; Möller, HJ. (2002). "World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders". World J Biol Psychiatry. 3 (4): 171–99. PMID 12516310. {{cite journal}}: Unknown parameter |month= ignored (help)
  19. ^ NetDoctor (October 1, 2006). "Xanax". netdoctor.co.uk. Retrieved 2 August 2007.
  20. ^ The British National Formulary (2007). "Alprazolam". BNF. Retrieved 2 August 2007.
  21. ^ Warner MD (1988). "Alprazolam as an antidepressant". J Clin Psychiatry. 49 (4): 148–50. PMID 3281931. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  22. ^ Sethy, Vh; Hodges, Dh, Jr (1982). "Role of beta-adrenergic receptors in the antidepressant activity of alprazolam". Research communications in chemical pathology and pharmacology. 36 (2): 329–32. PMID 6285432. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Lader, Mh (9 December 1985). "Treatment of affective disorders" (Free full text). British journal of clinical pharmacology. 19 (Suppl 1): 29S–30S. PMC 1463505. PMID 2859875.
  24. ^ Johnson, Da (9 December 1985). "The use of benzodiazepines in depression" (Free full text). British journal of clinical pharmacology. 19 (Suppl 1): 31S–35S. PMC 1463500. PMID 2859876.
  25. ^ Kostowski W, Malatyńska E, Płaźnik A, Dyr W, Danysz W (1986). "Comparative studies on antidepressant action of alprazolam in different animal models". Pol J Pharmacol Pharm. 38 (5–6): 471–81. PMID 2883637.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Srisurapanont, M; Boonyanaruthee, V (1997). "Alprazolam and standard antidepressants in the treatment of depression: a meta-analysis of the antidepressant effect". Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 80 (3): 183–8. PMID 9175386. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Brasfield, Kh (1991). "Practical psychopharmacologic considerations in depression". The Nursing clinics of North America. 26 (3): 651–63. PMID 1891399. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ Hubain, Pp; Castro, P; Mesters, P; De, Maertelaer, V; Mendlewicz, J (1990). "Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study". Journal of affective disorders. 18 (1): 67–73. doi:10.1016/0165-0327(90)90118-R. PMID 2136871. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  29. ^ Lydiard, Rb; Laraia, Mt; Ballenger, Jc; Howell, Ef (1987). "Emergence of depressive symptoms in patients receiving alprazolam for panic disorder". The American journal of psychiatry. 144 (5): 664–5. PMID 3578580. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ a b Rawson NS, Rawson MJ (1999). "Acute adverse event signalling scheme using the Saskatchewan Administrative health care utilization datafiles: results for two benzodiazepines". Can J Clin Pharmacol. 6 (3): 159–66. PMID 10495368.
  31. ^ a b "Alprazolam – Complete medical information regarding this treatment of anxiety disorders on MedicineNet.com". medicinenet.com. Retrieved 2 August 2007.
  32. ^ a b c Michel L, Lang JP (2003). "[Benzodiazepines and forensic aspects]". Encephale (in French). 29 (6): 479–85. PMID 15029082.
  33. ^ Kravitz HM, Fawcett J, Newman AJ (1993). "Alprazolam and depression: a review of risks and benefits". J Clin Psychiatry. 54 (Suppl): 78–84, discussion 85. PMID 8262892. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Hori A (1998). "Pharmacotherapy for personality disorders". Psychiatry Clin. Neurosci. 52 (1): 13–9. doi:10.1111/j.1440-1819.1998.tb00967.x. PMID 9682928. {{cite journal}}: Unknown parameter |month= ignored (help)
  35. ^ a b "alprazolam Side Effects, Interactions and Information - Drugs.com". drugs.com. Retrieved 2 August 2007.
  36. ^ "Complete Alprazolam information from Drugs.com". drugs.com. Retrieved 2 August 2007.
  37. ^ Cassano GB, Toni C, Petracca A; et al. (1994). "Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo". Eur Neuropsychopharmacol. 4 (1): 47–53. doi:10.1016/0924-977X(94)90314-X. PMID 8204996. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Münte TF, Gehde E, Johannes S, Seewald M, Heinze HJ (1996). "Effects of alprazolam and bromazepam on visual search and verbal recognition memory in humans: a study with event-related brain potentials". Neuropsychobiology. 34 (1): 49–56. doi:10.1159/000119291. PMID 8884760.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  39. ^ a b Barbee, Jg (1993). "Memory, benzodiazepines, and anxiety: integration of theoretical and clinical perspectives". The Journal of clinical psychiatry. 54 (Suppl): 86–97, discussion 98–101. PMID 8262893. {{cite journal}}: Unknown parameter |month= ignored (help)
  40. ^ "ALPRAZOLAM - ORAL (Xanax) side effects, medical uses, and drug interactions". medicinenet.com. Retrieved 2 August 2007.
  41. ^ Elie R, Lamontagne Y (1984). "Alprazolam and diazepam in the treatment of generalized anxiety". J Clin Psychopharmacol. 4 (3): 125–9. doi:10.1097/00004714-198406000-00002. PMID 6145726. {{cite journal}}: Unknown parameter |month= ignored (help)
  42. ^ Evans SM, Foltin RW, Fischman MW (1999). "Food "cravings" and the acute effects of alprazolam on food intake in women with premenstrual dysphoric disorder". Appetite. 32 (3): 331–49. doi:10.1006/appe.1998.0222. PMID 10336792. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  43. ^ Noyes R, DuPont RL, Pecknold JC; et al. (1988). "Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. II. Patient acceptance, side effects, and safety". Arch. Gen. Psychiatry. 45 (5): 423–8. PMID 3358644. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  44. ^ Béchir M, Schwegler K, Chenevard R; et al. (2007). "Anxiolytic therapy with alprazolam increases muscle sympathetic activity in patients with panic disorders". Auton Neurosci. 134 (1–2): 69–73. doi:10.1016/j.autneu.2007.01.007. PMID 17363337. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  45. ^ Rapaport, M; Braff, Dl (1985). "Alprazolam and hostility". The American journal of psychiatry. 142 (1): 146. PMID 2857070. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  46. ^ Arana, Gw; Pearlman, C; Shader, Ri (1985). "Alprazolam-induced mania: two clinical cases". The American journal of psychiatry. 142 (3): 368–9. PMID 2857534. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ Strahan A, Rosenthal J, Kaswan M, Winston A (1985). "Three case reports of acute paroxysmal excitement associated with alprazolam treatment". Am J Psychiatry. 142 (7): 859–61. PMID 2861755. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  48. ^ Reddy J, Khanna S, Anand U, Banerjee A (1996). "Alprazolam-induced hypomania". Aust N Z J Psychiatry. 30 (4): 550–2. doi:10.3109/00048679609065031. PMID 8887708. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  49. ^ a b Stahl, Stephen (1996). Essential Pharmacology: Neuroscientific Basis and Practical Applications. Cambridge: Cambridge University Press. ISBN 0-521-42620-0.
  50. ^ Juergens, Sm; Morse, Rm (1988). "Alprazolam dependence in seven patients". The American journal of psychiatry. 145 (5): 625–7. PMID 3258735. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  51. ^ Klein, E (2002). "The role of extended-release benzodiazepines in the treatment of anxiety: a risk-benefit evaluation with a focus on extended-release alprazolam". The Journal of clinical psychiatry. 63 (Suppl 14): 27–33. PMID 12562116.
  52. ^ Professor Heather Ashton (2002). "The Ashton Manual – Benzodiazepines: How They Work and How to Withdraw". benzo.org.uk. Retrieved 2008-10-31.
  53. ^ Dr JG McConnell (2007). "The Clinicopharmacotherapeutics of Benzodiazepine and Z drug dose Tapering Using Diazepam". bcnc. Retrieved 2008-10-31. {{cite web}}: Unknown parameter |month= ignored (help)
  54. ^ Closser, Mh; Brower, Kj (1994). "Treatment of alprazolam withdrawal with chlordiazepoxide substitution and taper". Journal of substance abuse treatment. 11 (4): 319–23. doi:10.1016/0740-5472(94)90042-6. PMID 7966502. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  55. ^ Romach MK, Somer GR, Sobell LC, Sobell MB, Kaplan HL, Sellers EM (1992). "Characteristics of long-term alprazolam users in the community". J Clin Psychopharmacol. 12 (5): 316–21. doi:10.1097/00004714-199210000-00004. PMID 1479048. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  56. ^ Fyer AJ (1987). "Discontinuation of Alprazolam Treatment in Panic Patients". Am J Psychiatry. 144 (3). benzo.org.uk: 303–8. PMID 3826428. Retrieved 10 December 2008. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  57. ^ Risse SC (1990). "Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder". The Journal of clinical psychiatry. 51 (5): 206–9. PMID 2335496. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  58. ^ Breier, A; Charney, Ds; Nelson, Jc (1984). "Seizures induced by abrupt discontinuation of alprazolam". The American journal of psychiatry. 141 (12): 1606–7. PMID 6150649. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  59. ^ Noyes R, Perry PJ, Crowe RR; et al. (1986). "Seizures following the withdrawal of alprazolam". J. Nerv. Ment. Dis. 174 (1): 50–2. doi:10.1097/00005053-198601000-00009. PMID 2867122. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  60. ^ Levy AB (1984). "Delirium and seizures due to abrupt alprazolam withdrawal: case report". J Clin Psychiatry. 45 (1): 38–9. PMID 6141159.
  61. ^ a b Haque W, Watson DJ, Bryant SG (1990). "Death following suspected alprazolam withdrawal seizures: a case report". Tex Med. 86 (1): 44–7. PMID 2300914.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  62. ^ Schatzberg, Alan (2003). Manual of Clinical Psychopharmacology. Washington, DC: American Psychiatric Pub. pp. 328–331. ISBN 1-58562-209-5. {{cite book}}: Unknown parameter |coauthor= ignored (|author= suggested) (help)
  63. ^ Higgitt, A; Fonagy, P; Lader, M (1988). "The natural history of tolerance to the benzodiazepines". Psychological medicine. Monograph supplement. 13: 1–55. doi:10.1017/S0264180100000412. PMID 2908516.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  64. ^ Professor Heather Ashton (2002). "The Ashton Manual - Benzodiazepines: How They Work and How to Withdraw". {{cite web}}: Unknown parameter |month= ignored (help)
  65. ^ Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM.; Eschalier, A. (2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Ann Pharm Fr. 67 (6): 408–13. doi:10.1016/j.pharma.2009.07.001. PMID 19900604. {{cite journal}}: Unknown parameter |month= ignored (help)
  66. ^ Hori A. (1998). "Pharmacotherapy for personality disorders". Psychiatry and clinical neurosciences. 52 (1): 13–9. doi:10.1111/j.1440-1819.1998.tb00967.x. PMID 9682928. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help); Unknown parameter |month= ignored (help)
  67. ^ Gardner DL, Cowdry RW (1985). "Alprazolam-induced dyscontrol in borderline personality disorder". Am J Psychiatry. 142 (1): 98–100. PMID 2857071. {{cite journal}}: Unknown parameter |month= ignored (help)
  68. ^ "Alprazolam". British National Formulary. 2007. Retrieved 3 August 2007.
  69. ^ mentalhealth.com (2007). "Alprazolam". Retrieved 3 August 2007.
  70. ^ "Xanax (Alprazolam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList". USA: RxList.com. 2008. p. 4. {{cite web}}: Unknown parameter |month= ignored (help)
  71. ^ García-Algar O (2007). "Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis". Clinical toxicology (Philadelphia, Pa.). 45 (3): 295–8. doi:10.1080/15563650601072191. PMID 17453885. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  72. ^ Oo CY (1995). "Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk". British journal of clinical pharmacology. 40 (3): 231–6. PMC 1365102. PMID 8527284. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  73. ^ DataBank, Inc (2008). "Xanax (Alprazolam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList". RxList. p. 8. Retrieved 7 December 2008. {{cite web}}: Unknown parameter |month= ignored (help)
  74. ^ a b "ALPRAZOLAM - ORAL (Xanax) side effects, medical uses, and drug interactions". MedicineNet. 2005. Retrieved 7 December 2008. {{cite web}}: Unknown parameter |month= ignored (help)
  75. ^ Kozená L (1995). "Vigilance impairment after a single dose of benzodiazepines". Psychopharmacology (Berl). 119 (1): 39–45. doi:10.1007/BF02246052. PMID 7675948. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  76. ^ Iqbal, MM.; Sobhan, T.; Ryals, T. (2002). "Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant". Psychiatr Serv. 53 (1): 39–49. PMID 11773648. {{cite journal}}: Unknown parameter |month= ignored (help)
  77. ^ Einarson A, Selby P, Koren G (2001). "Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling" (PDF). J Psychiatry Neurosci. 26 (1): 44–8. PMC 1408034. PMID 11212593. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  78. ^ Skelton KH (October 20, 2004). "Spontaneous withdrawal from the triazolobenzodiazepine alprazolam increases cortical corticotropin-releasing factor mRNA expression". J Neurosci. 24 (42): 9303–12. doi:10.1523/JNEUROSCI.1737-04.2004. PMID 15496666. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  79. ^ Chouinard G (2004). "Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound". J Clin Psychiatry. 65 (Suppl 5): 7–12. PMID 15078112.
  80. ^ White, G; Gurley, Da (1995). "Alpha subunits influence Zn block of gamma 2 containing GABAA receptor currents". Neuroreport. 6 (3): 461–4. doi:10.1097/00001756-199502000-00014. PMID 7766843. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  81. ^ Arvat, E.; Giordano, R.; Grottoli, S.; Ghigo, E. (2002). "Benzodiazepines and anterior pituitary function". J Endocrinol Invest. 25 (8): 735–47. PMID 12240908. {{cite journal}}: Unknown parameter |month= ignored (help)
  82. ^ Mandrioli, R.; Mercolini, L.; Raggi, MA. (2008). "Benzodiazepine metabolism: an analytical perspective". Curr Drug Metab. 9 (8): 827–44. PMID 18855614. {{cite journal}}: Unknown parameter |month= ignored (help)
  83. ^ a b Greenblatt, Dj; Wright, Ce (1993). "Clinical pharmacokinetics of alprazolam. Therapeutic implications". Clinical pharmacokinetics. 24 (6): 453–71. doi:10.2165/00003088-199324060-00003. PMID 8513649. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  84. ^ Otani, K. (2003). "[Cytochrome P450 3A4 and Benzodiazepines]". Seishin Shinkeigaku Zasshi. 105 (5): 631–42. PMID 12875231.
  85. ^ Dresser, GK.; Spence, JD.; Bailey, DG. (2000). "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition". Clin Pharmacokinet. 38 (1): 41–57. PMID 10668858. {{cite journal}}: Unknown parameter |month= ignored (help)
  86. ^ Wang JS, DeVane CL (2003). "Pharmacokinetics and drug interactions of the sedative hypnotics" (PDF). Psychopharmacol Bull. 37 (1): 10–29. PMID 14561946.
  87. ^ "AD535DF9-6361-460D-9648-450A0A6F61CD.xml". {{cite journal}}: |access-date= requires |url= (help); |contribution= ignored (help); Cite has empty unknown parameters: |coeditors= and |coauthors= (help); Cite journal requires |journal= (help)
  88. ^ Back DJ (1990). "Pharmacokinetic drug interactions with oral contraceptives". Clin Pharmacokinet. 18 (6): 472–84. doi:10.2165/00003088-199018060-00004. PMID 2191822. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  89. ^ Izzo, AA.; Ernst, E. (2001). "Interactions between herbal medicines and prescribed drugs: a systematic review". Drugs. 61 (15): 2163–75. PMID 11772128.
  90. ^ Izzo, AA. (2004). "Drug interactions with St. John's Wort (Hypericum perforatum): a review of the clinical evidence". Int J Clin Pharmacol Ther. 42 (3): 139–48. PMID 15049433. {{cite journal}}: Unknown parameter |month= ignored (help)
  91. ^ Madabushi, R.; Frank, B.; Drewelow, B.; Derendorf, H.; Butterweck, V. (2006). "Hyperforin in St. John's wort drug interactions". Eur J Clin Pharmacol. 62 (3): 225–33. doi:10.1007/s00228-006-0096-0. PMID 16477470. {{cite journal}}: Unknown parameter |month= ignored (help)
  92. ^ Izzo, AA.; Ernst, E. (2009). "Interactions between herbal medicines and prescribed drugs: an updated systematic review". Drugs. 69 (13): 1777–98. doi:10.2165/11317010-000000000-00000. PMID 19719333.
  93. ^ Griffiths RR, Wolf B (1990). "Relative abuse liability of different benzodiazepines in drug abusers". J Clin Psychopharmacol. 10 (4): 237–43. doi:10.1097/00004714-199008000-00002. PMID 1981067. {{cite journal}}: Unknown parameter |month= ignored (help)
  94. ^ Eric C (2006). "MR Findings of Alprazolam Injection into the Femoral Artery with Microembolization and Rhabdomyolysis" (pdf). Radiology Case Reports. 1 (3). {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  95. ^ "DB00404 (Alprazolam)". Canada: DrugBank. August 26, 2008.
  96. ^ Sheehan MF, Sheehan DV, Torres A, Coppola A, Francis E (1991). "Snorting benzodiazepines". Am J Drug Alcohol Abuse. 17 (4): 457–68. doi:10.3109/00952999109001605. PMID 1684083.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  97. ^ Soumerai SB, Simoni-Wastila L, Singer C; et al. (2003). "Lack of relationship between long-term use of benzodiazepines and escalation to high dosages". Psychiatr Serv. 54 (7): 1006–11. doi:10.1176/appi.ps.54.7.1006. PMID 12851438. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  98. ^ Walker, Bm; Ettenberg, A (2003). "The effects of alprazolam on conditioned place preferences produced by intravenous heroin". Pharmacology, biochemistry, and behavior. 75 (1): 75–80. doi:10.1016/S0091-3057(03)00043-1. PMID 12759115. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  99. ^ MARCIA LANE (29 September 2006). "Xanax, alcohol mix kills 2". USA: St. Augustine Record. Retrieved 10 December 2008.
  100. ^ Wright State University and the University of Akron (January 2008). "OSAM - O- GRAM Highlights of Statewide Drug Use Trends" (PDF). USA: Ohio Government. Retrieved 10 December 2008.
  101. ^ Detective Eladio M. Paez (15 June 2008). "STATEMENT ON RAVES AND CLUB DRUGS TO THE SUBCOMMITTEE ON CRIME, CONGRESS OF THE UNITED STATES, HOUSE OF REPRESENTATIVES". USA: GOV House Judiciary. Retrieved 10 December 2008.
  102. ^ "SURVEILLANCE OF DRUG ABUSE TRENDS IN THE STATE OF OHIO - A Report Prepared for the Ohio Department of Alcohol and Drug Addiction Services". USA: The Ohio Substance Abuse Monitoring Network. 31 July 2001. Retrieved 10 December 2008.
  103. ^ "Microgram bulletin". US DEA.
  104. ^ Ballenger, Jc (1984). "Psychopharmacology of the anxiety disorders". The Psychiatric clinics of North America. 7 (4): 757–71. PMID 6151647. {{cite journal}}: Unknown parameter |month= ignored (help)
  105. ^ Evans, Sm; Levin, Fr; Fischman, Mw (2000). "Increased sensitivity to alprazolam in females with a paternal history of alcoholism". Psychopharmacology. 150 (2): 150–62. doi:10.1007/s002130000421. PMID 10907668. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  106. ^ Streeter, Cc; Ciraulo, Da; Harris, Gj; Kaufman, Mj; Lewis, Rf; Knapp, Cm; Ciraulo, Am; Maas, Lc; Ungeheuer, M; Szulewski, S; Renshaw, Pf (1998). "Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism". Psychiatry research. 82 (2): 69–82. doi:10.1016/S0925-4927(98)00009-2. PMID 9754450. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  107. ^ Ciraulo, Da; Sarid-Segal, O; Knapp, C; Ciraulo, Am; Greenblatt, Dj; Shader, Ri (1996). "Liability to alprazolam abuse in daughters of alcoholics". The American journal of psychiatry. 153 (7): 956–8. PMID 8659624. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  108. ^ Ciraulo, Da; Barnhill, Jg; Greenblatt, Dj; Shader, Ri; Ciraulo, Am; Tarmey, Mf; Molloy, Ma; Foti, Me (1988). "Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men". The Journal of clinical psychiatry. 49 (9): 333–7. PMID 3417618. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  109. ^ Vorma, H; Naukkarinen, Hh; Sarna, Sj; Kuoppasalmi, Ki (2005). "Predictors of benzodiazepine discontinuation in subjects manifesting complicated dependence". Substance use & misuse. 40 (4): 499–510. doi:10.1081/JA-200052433. PMID 15830732.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  110. ^ Isbister GK, O'Regan L, Sibbritt D, Whyte IM (2004). "Alprazolam is relatively more toxic than other benzodiazepines in overdose". Br J Clin Pharmacol. 58 (1): 88–95. doi:10.1111/j.1365-2125.2004.02089.x. PMC 1884537. PMID 15206998. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  111. ^ Wolf BC, Lavezzi WA, Sullivan LM, Middleberg RA, Flannagan LM (2005). "Alprazolam-related deaths in Palm Beach County". Am J Forensic Med Pathol. 26 (1): 24–7. doi:10.1097/01.paf.0000153994.95642.c1. PMID 15725773.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  112. ^ Rogers, Wo; Hall, Ma; Brissie, Rm; Robinson, Ca (1997). "Detection of alprazolam in three cases of methadone/benzodiazepine overdose". Journal of forensic sciences. 42 (1): 155–6. PMID 8988593. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  113. ^ Jones AW, Holmgren A, Kugelberg FC. Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results. Ther. Drug Monit. 29: 248-260, 2007.
  114. ^ Fraser AD, Bryan W. Evaluation of the Abbott ADx and TDx serum benzodiazepine immunoassays for analysis of alprazolam. J. Anal. Toxicol. 15: 63-65, 1991.
  115. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 45-48.
  116. ^ Merck Manual (5 February 2009). "alprazolam". Unbound Medicine. Retrieved 10 March 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  117. ^ "Benzodiazepine Names". non-benzodiazepines.org.uk. Retrieved 2008-10-31.
  118. ^ "DEA, Drug Scheduling". DEA. Retrieved 2008-10-31.
  119. ^ UK Gov (1991). "Misuse of Drugs Act 1971 (c. 38)". The UK Statute Law database.
  120. ^ International Narcotics Control Board (2003). "List of psychotropic substances under international control" (PDF). incb.org. Retrieved 7 December 2008. {{cite web}}: Unknown parameter |month= ignored (help)
  121. ^ "Misuse Of Drugs (Amendment) Regulations". Irish Statute Book. Office of the Attorney General. 1993.
  122. ^ ____284.aspx Narkotikaklassade läkemedel, Läkemedelsverket

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Alprazolam&oldid=371392964"