Alprazolam 243513 225749404 2008-07-15T05:59:51Z Djsasso 149061 Reverted edits by [[Special:Contributions/202.125.143.75|202.125.143.75]] to last version by 71.212.39.81 (using [[WP:HG|Huggle]]) {{Drugbox| | IUPAC_name = 8-chloro-1-methyl-6-phenyl-4H-<br>[1,2,4]triazolo[4,3-a][1,4]benzodiazepine | image = Alprazolam.svg | width = 150 | image2 = Alprazolam3d.png | CAS_number = 28981-97-7 | ATC_prefix = N05 | ATC_suffix = BA12 | ATC_supplemental = | PubChem = 2118 | DrugBank = APRD00280 | C=17 | H=13 | Cl=1 | N=4 | molecular_weight = 308.765 | bioavailability = 80-90% | metabolism = [[Liver|Hepatic]], via [[Cytochrome P450 3A4]] | elimination_half-life = ''Immediate release:'' 11.2 hours;<ref>[http://www.rxlist.com/cgi/generic/alpraz_cp.htm Xanax (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList<!-- Bot generated title -->]</ref> ''Extended release:'' 10.7-15.8 hours<ref>[http://www.rxlist.com/cgi/generic/xanax-xr_cp.htm Xanax XR (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList<!-- Bot generated title -->]</ref> | excretion = [[Kidney|Renal]] | pregnancy_US = D | legal_US = Schedule IV | routes_of_administration = Oral }} '''Alprazolam''', also known under the [[#Availability|trade names]] '''Xanax''' and '''Niravam''', is a short-acting drug of the [[benzodiazepine]] class used to treat moderate to severe [[anxiety disorder]]s, [[panic attack]]s, and as an adjunctive treatment for anxiety associated with [[clinical depression]]. It is also available in an [[extended release]] form, '''Xanax XR'''. Both forms are now available generically. ==History== "[The public often] underestimate the extent to which certain disorders affect the general populace. When you treat them, it can make a tremendous amount of difference in their lives." (David Sheehan, ''first discovered alprazolam's efficacy in treating [[panic disorder]].<ref>[http://www.research.usf.edu/absolutenm/templates/newro.asp?articleid=363&zoneid=4 Research.Online - University of South Florida's Research Guide<!-- Bot generated title -->]</ref>'') Alprazolam was first [[Chemical synthesis|synthesize]]d by [[Upjohn]] (now a part of [[Pfizer]]). Its patent (#3,987,052)<ref>[http://patft.uspto.gov/netacgi/nph-Parser?patentnumber=3,987,052 Patent 3,987,052]</ref> was filed on [[October 29]], [[1969]], granted on [[October 19]], [[1976]] and expired in September 1993. It was released in [[1981]].<ref>[http://thephoenix.com/article_ektid51411.aspx Xanax junkies - News - The Phoenix<!-- Bot generated title -->]</ref><ref>1981 ''American Journal of Psychiatry'' contains advertisements for Xanax as an available drug.</ref> The first indication for which alprazolam was approved was panic disorder. Upjohn took this direction at the behest of a young [[psychiatrist]] David Sheehan. Sheehan's suggestion was to use the confusion [[Diagnostic and Statistical Manual of Mental Disorders|DSM-III]] created in the classification of anxiety disorders (a distinction had just been made in DSM-III between [[generalized anxiety disorder]] (GAD) and [[panic disorder]]). 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 well responding to benzodiazepines. He suggested to Upjohn that marketing alprazolam for panic disorder will both cover new diagnostic territory and stress the unique potency of this drug. Sheehan describes that the first group of patients treated by alprazolam was so impressed by its action that they knew outright—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 FDA, they sold out and made a profit.<ref name="isbn0-340-761105">{{cite book |author=Healy, David |title=The Psychopharmacologists, Vol. III: Interviews |publisher=Arnold|location=London|year=2000|pages=479-504|isbn=0-340-761105 |oclc= |doi=}}</ref> ==Pharmacology== Alprazolam is a ''triazolobenzodiazepine'',<ref>J Med. Chem. Vol. 14, p. 1078-1081 (1971) DOI: 10.1021/jm00293a015</ref> that is, a benzodiazepine with a triazolo-ring attached to its structure. Benzodiazepines produce a variety of effects by modulating the [[GABA A receptor|GABA<sub>A</sub>]] subtype of the [[GABA receptor]], the most prolific inhibitory receptor within the brain. The GABA<sub>A</sub> receptor is made up from 5 subunits out of a possible 19, and GABA<sub>A</sub> receptors made up of different combinations of subunits have different properties, different locations within the brain and importantly, different activities in regards to benzodiazepines. In order for GABA<sub>A</sub> receptors to be sensitive to the action of benzodiazepines they need to contain an α and a γ subunit, where the benzodiazepine binds. Once bound, the benzodiazepine locks the GABA<sub>A</sub> receptor into a conformation where the neurotransmitter GABA has much higher affinity for the GABA<sub>A</sub> receptor, increasing the frequency of opening of the associated Chloride ion channel and hyperpolarising the membrane. This potentiates the inhibitory effect of the available GABA leading to sedatory and anxiolytic effects. As mentioned, different benzodiazepines can have different affinities for GABA<sub>A</sub> receptors made up of different collection of subunits. For instance, benzodiazepines with high activity at the α1 are associated with [[sedation]] whereas those with higher affinity for GABA<sub>A</sub> receptors containing α2 and/or α3 subunits have greater [[anxiolytic]] activity. The binding site for benzodiazepines is distinct from the binding site for [[barbiturate]]s and GABA on the GABA receptor. There is some evidence for [[antidepressant]] treatment of [[clinical depression]] in outpatient settings, evidence for inpatients is lacking;<ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3281931&dopt=Abstract Alprazolam as an antidepressant. J Clin Psychiatry. 1988&#93; - PubMed Result<!-- Bot generated title -->]</ref> other benzodiazepines are not known to have antidepressant activity. ==Pharmacokinetics== Alprazolam is readily absorbed from the gastrointestinal tract. The peak [[blood plasma|plasma]] concentration is achieved in 1-2 hours. Most of the drug is bound to plasma protein, mainly [[serum albumin]]. Alprazolam is [[hydroxylation|hydroxylated]] in the liver to α-hydroxyalprazolam, which is also pharmacologically active. This and other [[metabolite]]s are later excreted in urine as [[glucuronide]]s. Some of the drug is also excreted in unchanged form. ==Indications== [[Image:Alprazolam2mgresize.jpg|thumb|right|120px|alprazolam 2mg tablet bottle]] The main medical uses for alprazolam include: * 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 preventing moderate to severe anxiety, [[essential tremor]], panic attacks and other types of convulsive behaviors. Physicians who 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.<ref>{{cite web |url = http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf |title = FDA APPROVED LABELING FOR XANAX XR |accessdaymonth = 2nd Aug |accessyear = 2007 |date=23rd |year = 2003 |month = Jan |author = FDA |format = pdf |publisher = Federal Drug Administration |pages = 4 |quote = The longer-term efficacy of XANAX XR has not been systematically evaluated. Thus, the physician who elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.}}</ref> However, long-term maintenance therapy on alprazolam is not unheard-of in the medical community, and, if a genuine therapeutic need exists, benefits must be weighed against risks. * Alprazolam is recommended for the short-term treatment (2-4 weeks) of severe acute anxiety. Alprazolam should only ''very rarely'' be used for longer periods of time -- the body becomes rapidly tolerant to the drug's effects, which may translate to decreased efficacy.<ref>{{cite web |url = http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf |title = Xanax |accessdaymonth = 2nd Aug |accessyear = 2007 |date=23rd |year = 2006 |month = Oct |date=1 |author = NetDoctor |publisher = netdoctor.co.uk }}</ref><ref>{{cite web |url = http://www.bnf.org/bnf/bnf/53/3173.htm |title = Alprazolam |accessdaymonth = 2nd Aug |accessyear = 2007 |year = 2007 |author = The British National Formulary |publisher = BNF }}</ref> Decreased efficacy can lead to dose escalation, and the use of high doses puts the patient at higher risk for withdrawal if the drug is discontinued suddenly. * However, in 1992 Romach and colleagues reported that dose escalation was '''not''' a characteristic of long-term alprazolam users, and the majority of patients indicated that alprazolam continued to be effective.<ref> {{cite journal |author=Romach MK, Somer GR, Sobell LC, Sobell MB, Kaplan HL, Sellers EM |title=Characteristics of long-term alprazolam users in the community |journal=J Clin Psychopharmacol |volume=12 |issue=5 |pages=316–21 |year=1992 |pmid=1479048|doi=10.1097/00004714-199210000-00004}} </ref> A 2003 study did not support the hypothesis that long-term use of benzodiazepines frequently results in notable dose escalation.<ref> {{cite journal |author=Soumerai SB, Simoni-Wastila L, Singer C, ''et al'' |title=Lack of relationship between long-term use of benzodiazepines and escalation to high dosages |journal=Psychiatr Serv |volume=54 |issue=7 |pages=1006–11 |year=2003 |pmid=12851438|doi=10.1176/appi.ps.54.7.1006}} </ref>In a 1-year follow-up study of patients with panic disorder continuing treatment with clonazepam, 90% maintained a positive response without developing significant tolerance. In a 2.5-year follow-up study of alprazolam therapy, little evidence of tolerance emerged.<ref name="pmid1970813">{{cite journal |author=Pollack MH |title=Long-term management of panic disorder |journal=J Clin Psychiatry |volume=51 Suppl |issue= |pages=11–3; discussion 50–3 |year=1990 |pmid=1970813 |doi=}}</ref> ==Availability== [[Image:XanaxHologramAd.png|thumb|100px|right|Holographic advertisement for Xanax, 1989.]] {{Unreferencedsection|date=May 2008}} Xanax is the main and most commonly known brand name for Alprazolam. There is a large variety of generic brand names for Alprazolam in use throughout the world. In English-speaking countries, Alprazolam is sold under the following brand names: '''Aloram, Alprax, Alprox, Alzam, Anxirid, Apo-Alpraz, Azor, Calmax, Frontal, Frontin, Gerax, Helex, Kalma, Kinax, Neurol, Novo-Alprazol, Nu-Alpraz, Restyl, Trankimazin, Xanax, Xanor, Zopax, Trika'''. It is also commonly known as "Handles", "T-Bars", "White Tees", "Xanies (Pronounced ZAN-eez)", "Sticks", "Totem Poles", "Ladders", "Bars", "Yellow Buses", "French Fries", "Footballs" and "Paint Thinner" when laced, when sold or used illicitly. ==Packaging== [[Image:Xanax DOJ.jpg|frame|right]] Imprints vary depending on drug manufacturer. The imprints above refer to the name-brand design in the United States and other [[first world]] countries,<ref>[http://www.drugs.com/forum/topic.asp?TOPIC_ID=7955 BENZODIAZEPINE Imprints - Drugs.com<!-- Bot generated title -->]</ref> however, every variety of alprazolam is generically available and thus individual pill design is left up to the manufacturer. ==Side effects== Side effects of alprazolam may occur in patients and are more likely the higher the dosage taken. If signs of an allergic reaction occur such as [[hives]], difficulty breathing, [[swelling]] of face, lips, tongue or throat occur medical attention should be sought immediately. Medical attention should also be sought immediately if signs of [[jaundice]] appear such as [[yellowing]] of the skin or eyes. Other side effects which may occur are as follows:<ref>{{cite web |url = http://alprazolam.drugs.com/ |title = Complete Alprazolam information from Drugs.com |accessdaymonth = 2nd Aug |accessyear = 2007 |publisher = drugs.com }}</ref><ref>{{cite web |url = http://www.medicinenet.com/alprazolam-oral/article.htm |title = ALPRAZOLAM - ORAL (Xanax) side effects, medical uses, and drug interactions. |accessdaymonth = 2nd Aug |accessyear = 2007 |publisher = medicinenet.com}}</ref><ref>{{cite web |url = http://www.medicinenet.com/alprazolam/article.htm |title = Alprazolam – Complete medical information regarding this treatment of anxiety disorders on MedicineNet.com |accessdaymonth = 2nd Aug |accessyear = 2007 |publisher = medicinenet.com}}</ref><ref>{{cite web |url = http://www.drugs.com/Alprazolam/index.html |title = alprazolam Side Effects, Interactions and Information - Drugs.com |accessdaymonth = 2nd Aug |accessyear = 2007 |publisher = drugs.com}}</ref> * [[drowsiness]] * decreased inhibitions, no fear of danger (increased risk taking behavior) * [[depressed mood]] with thoughts of [[suicide]] or [[self harm]] * [[hallucinations]], [[agitation]] and [[hostility]] * [[hyperactivity]] * feeling [[dizziness]], [[light headed]] or [[fainting]] * urinating less than usual or not at all * [[headache]], [[fatigue (medical)|fatigue]], [[joint pain]] and unusual weakness (flu like symptoms) * [[speech problems]], * complete memory loss, ([[amnesia]]) and [[concentration]] problems * changes in appetite (including changes in weight) * blurred vision, unsteadiness and [[Dyspraxia|clumsiness]] (impaired [[coordination]] and balance) * [[constipation]], [[diarrhea]], [[nausea]] and [[vomiting]] * decreased sex drive * [[dry mouth]] or increased [[salivation]] * [[nervousness]], [[restlessness]], [[sleeplessness]] (insomnia) and [[sweating]] * pounding in the chest or rapid heartbeat * skin inflammation * [[muscle twitching]], [[tremor]] and seizure ([[convulsions]]) ==Physical dependence and withdrawal== {{See also|Benzodiazepine withdrawal syndrome}} There is a consensus among psychiatrists today that alprazolam and other benzodiazepines cause withdrawal symptoms after long-term treatment and discontinuation should be done gradually over a period of months (or even up to a year) to avoid serious withdrawal symptoms such as agitation, panic attacks, rebound anxiety, muscle cramps and [[seizure]]s.{{Fact|date=August 2007}} Some patients on alprazolam (Xanax) may benefit from a substitution with [[diazepam]] (Valium) or [[chlordiazepoxide]] (Librium) as these drugs remain in the bloodstream longer and therefore have less potential for abuse and dependence. There is a higher chance of withdrawal symptoms if the drug is administered in a higher dosage than recommended, or if a patient stops taking the medication altogether without slowly helping your body wean itself off the drug. If you feel the need to end treatment with alprazolam, consult your doctor/physician before discontinuing medication. Some immediate symptoms of alprazolam withdrawal include: '''Common Withdrawal Symptoms''' * A rapid/random heartbeat ([[Tachycardia]]) * [[Depression (mood)|Depression]] * [[Dry mouth]]/[[chapped lips]] * Temporary inability to stop talking/moving ([[OCD]]) * Mental sensitivity * Strong [[loss of appetite]] * Extreme [[Insomnia]] * [[Anxiety]] * [[Dizziness]] * Minor [[tremors]] '''Possible/Less Common Withdrawal Symptoms''' * [[Nausea]], [[vomiting]], or [[diarrhea]] * [[Panic attack]]s * [[Mood swings]] * [[Heart palpitations]] * [[Hallucinations]] * [[Memory loss]] * [[Seizures]] * [[Fever]] Patients treated with alprazolam or other benzodiazepines for generalized anxiety disorder were found (when abruptly discontinuing their medication) to experience withdrawal symptoms such as a worsening of anxiety, as well as the development of physical withdrawal symptoms.<ref>{{cite journal |author=Chouinard G |coauthors=Labonte A, Fontaine R, Annable L |year=1983 |title=New concepts in benzodiazepine therapy: rebound anxiety and new indications for the more potent benzodiazepines |volume=7 |issue=4-6 |pages=669–73 |pmid=6141609 |journal=Prog Neuropsychopharmacol Biol Psychiatry |doi=10.1016/0278-5846(83)90043-X}}</ref> Patients taking a dosing regimen larger than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms, 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, rage reactions, hyperalertness, increased nightmares, and intrusive thoughts.<ref>{{cite journal |author=Risse SC |coauthors= Whitters A, Burke J, Chen S, [[Raymond Monsour Scurfield|Scurfield RM]], Raskind MA. |title=Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. |journal=The Journal of clinical psychiatry. |volume=51 |issue=5 |pages=206–9 |year=1990 |pmid=2335496}}</ref> After 8 - 9 weeks of alprazolam taken at a fixed prescribed dose, the following symptoms have been found to occur during abrupt discontinuation: dysphoric mood, fatigue, low energy, confusion, and elevated systolic blood pressure, severe anxiety.<ref>{{cite journal |journal=J Clin Psychopharmacol |year=2006 | month=Oct |volume=26 |issue=5 |pages=519–23 |title=Abrupt discontinuation of alprazolam and cognitive style in patients with panic disorder: early effects on mood, performance, and vital signs |author=Uhlenhuth EH |coauthors=Starcevic V, Qualls C, Antal EJ, Matuzas W, Javaid JI, Barnhill J |pmid=16974197}}</ref> When a patient discontinues use, they may experience the symptoms they had before taking medication. Symptoms may also be accompanied by other reactions including changes in mood, anxiety, or sleep. Rebound anxiety is usually a result of abrupt discontinuation of this medication; patients who taper off are less likely to experience these symptoms. [[Physical dependence]] is the major limiting factor against long-term use of alprazolam and other benzodiazepines. Factors which determine the severity of the [[benzodiazepine withdrawal syndrome]] experienced during dose reduction of alprazolam include:<ref name="physdep">{{cite journal |author=Wolf B |coauthors= Griffiths RR. |title= Physical dependence on benzodiazepines: differences within the class. |journal= Drug and alcohol dependence. |volume= 29 |issue= 2 |pages= 153–6 |year= 1991 |pmid= 1686752 |doi=10.1016/0376-8716(91)90044-Y}}</ref> * dosage * length of use * frequency of dosing * method of withdrawal<ref>[http://www.benzo.org.uk/manual/ The Ashton Manual - Benzodiazepines: How They Work and How to Withdraw by professor Heather Ashton]</ref> * 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 short-acting high potency benzodiazepines for example alprazolam or [[lorazepam]] Alprazolam has an exceptional history insofar soon after its introduction a large number of case reports were published in the [[medical literature]] of severe [[withdrawal symptoms]] related case reports of withdrawal psychoses, seizures and intense rebound anxiety upon discontinuation of alprazolam. In the [[United States]] a survey of [[physicians]] showed that 84% of physicians reported alprazolam as being extremely problematic in terms of the severity and prolonged nature of the [[benzodiazepine withdrawal syndrome]] after discontinuation. However, in 1993 the New England Journal of Medicine reported there is no reliable evidence to support the existence of a ''persistent'' benzodiazepine withdrawal syndrome, and this syndrome has been described only in anecdotal reports, with patients typically reporting "withdrawal" symptoms not present during or before benzodiazepine treatment that persist for many months or years after treatment is stopped. Experimental neuropharmacologic studies document that all the side effects of benzodiazepines, whether behavioral or neurochemical, disappear within several days or weeks after the drug is eliminated. The weight of evidence indicates that any new symptoms that persist for more than two months after the last dose of a benzodiazepine either are part of the premorbid condition or have appeared by coincidence or as a consequence of the natural history of the underlying illness.<ref> {{cite journal |author=Shader RI, Greenblatt DJ |title=Use of benzodiazepines in anxiety disorders |journal=N. Engl. J. Med. |volume=328 |issue=19 |pages=1398–405 |year=1993 |pmid=8292115 |url=http://content.nejm.org/cgi/content/full/328/19/1398?ijkey=f7d4b2ef05c438f7c8368f8f6406c233808157ac&keytype2=tf_ipsecsha |doi=10.1056/NEJM199305133281907}}</ref> The benzodiazepines [[diazepam]](Valium) and [[oxazepam]](Seresta) were found to produce less severe withdrawal symptoms than alprazolam(Xanax) or [[lorazepam]](Temesta/Ativan).<ref name="physdep">{{cite journal |author=Wolf B |coauthors= Griffiths RR. |title= Physical dependence on benzodiazepines: differences within the class. |journal= Drug and alcohol dependence. |volume= 29 |issue= 2 |pages= 153–6 |year= 1991 |pmid= 1686752 |doi=10.1016/0376-8716(91)90044-Y}}</ref> Alprazolam should never be abruptly discontinued 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 withdrawal,<ref name="pmid6141159">{{cite journal |author=Levy AB |title=Delirium and seizures due to abrupt alprazolam withdrawal: case report |journal=J Clin Psychiatry |volume=45 |issue=1 |pages=38–9 |year=1984 |pmid=6141159 |doi=}}</ref><ref name="pmid2300914">{{cite journal |author=Haque W, Watson DJ, Bryant SG |title=Death following suspected alprazolam withdrawal seizures: a case report |journal=Tex Med |volume=86 |issue=1 |pages=44–7 |year=1990 |pmid=2300914 |doi=}}</ref> and one death occurred from withdrawal-related seizures after gradual dose reduction.<ref name="pmid2300914"/> ==Contraindications== Use of alprazolam should be avoided, or carefully monitored by medical professionals, in individuals with the following conditions:<ref>{{cite web |url = http://www.bnf.org/bnf/bnf/53/3173.htm |title = Alprazolam |accessdaymonth = 3rd Aug |accessyear = 2007 |year = 2007 |publisher = British National Formulary}}</ref><ref>{{cite web |url = http://www.mentalhealth.com/drug/p30-x01.html |title = Alprazolam |accessdaymonth = 3rd Aug |accessyear = 2007 |author = mentalhealth.com |year = 2007}}</ref> * [[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 [[Episodic dyscontrol syndrome|dyscontrol]]),<ref>{{cite journal |author=Hori A. |coauthors= |title=Pharmacotherapy for personality disorders. |journal=Psychiatry and clinical neurosciences. |volume=52 |issue=1 |pages=13–9 |year=1998 |month=Feb |pmid=9682928 |doi=10.1111/j.1440-1819.1998.tb00967.x}}</ref> however [[correlation does not imply causation]], as these behaviors are seen in unmedicated [[Bipolar disorder|BPD]] patients. ===Overdose=== Overdoses can be mild to severe depending on how much of the drug is taken and if any other depressants have been taken. Xanax overdose reflect the central nervous system depression of the brain and may include one or more of the following symptoms: *[[Somnolence]] (difficulty staying awake) *Mental confusion *[[Hypotension]] *Impaired motor functions ** Impaired or absent reflexes ** Impaired balance ** Dizziness *[[Hypoventilation]] (Respiratory Depression) *[[Coma]] *[[Death]] 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 was attributed to alprazolam alone.<ref name="pmid15725773">{{cite journal |author=Wolf BC, Lavezzi WA, Sullivan LM, Middleberg RA, Flannagan LM |title=Alprazolam-related deaths in Palm Beach County |journal=Am J Forensic Med Pathol |volume=26 |issue=1 |pages=24–7 |year=2005 |pmid=15725773 |doi=}}</ref> ===Pregnancy=== Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam.<ref>[http://www.rxlist.com/cgi/generic/alpraz_wcp.htm#W Xanax (Alprazolam) drug warnings and precautions - prescription drugs and medications at RxList<!-- Bot generated title -->]</ref> If one is currently planning to become pregnant, one should discuss this and all medicines with their [[obstetrician]] or other doctor. ====Teratogenicity classification==== Marked [[Pregnancy category#United States|Pregnancy Category D]] by the U.S. [[FDA]]. ====Effects on the fetus==== It should be considered that the child born of a mother who is receiving benzodiazepines may be at risk of developing [[withdrawal symptoms]] from the drug during the postnatal period. Also, neonatal flaccidity and respiratory problems have been reported in children born of mothers who have been receiving benzodiazepines.<ref>{{cite journal |author=García-Algar O |coauthors= López-Vílchez MA, Martín I, Mur A, Pellegrini M, Pacifici R, Rossi S, Pichini S. |title=Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis. |journal=Clinical toxicology (Philadelphia, Pa.). |volume=45 |issue=3 |pages=295–8 |year=2007 |pmid=17453885}}</ref> ====Labor and delivery==== Alprazolam has no established use in labor or delivery. ====Nursing mothers (neonates)==== Benzodiazepines, including alprazolam are known to be excreted in human milk.<ref>{{cite journal |author=Oo CY |coauthors= Kuhn RJ, Desai N, Wright CE, McNamara PJ. |title=Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk. |journal=British journal of clinical pharmacology. |volume=40 |issue=3 |pages=231–6 |year=1995 |month=Sep |pmid=8527284}}</ref> Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.<ref>[http://www.rxlist.com/cgi/generic/alpraz_wcp.htm][http://www.medicinenet.com/alprazolam-oral/article.htm]</ref> As a general rule, nursing should not be undertaken by mothers who use alprazolam. ===Geriatric use=== 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.<ref>[http://www.medicinenet.com/alprazolam-oral/article.htm ALPRAZOLAM - ORAL (Xanax) side effects, medical uses, and drug interactions<!-- Bot generated title -->]</ref> ==Food and drug interactions== Eating grapefruits or drinking grapefruit juice while using alprazolam increases blood concentrations by inhibiting the intestinal metabolism.<ref>http://www.fhma.com/grapefruit.htm</ref> In fact, any drug that inhibits [[CYP3A4]], for which alprazolam is a substrate, will increase serum concentrations of alprazolam significantly if administered prior or concurrently. Tagamet ([[cimetidine]]) is a widely used H2 blocker antacid that inhibits numerous cytochrome P450 enzymes. Oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.<ref>{{cite journal | author = Back DJ | coauthors = Orme ML. | year = 1990 | month = Jun | title = Pharmacokinetic drug interactions with oral contraceptives. | journal = Clin Pharmacokinet. | volume = 18 | issue = 6 | pages = 472–84 | pmid = 2191822 }}</ref> ==Special precautions== Like all [[central nervous system]] [[depressants]], including [[alcohol]], alprazolam in doses of 0.5 mg and above can cause significant deterioration in [[alertness]], combined with increased feelings of sleepiness.<ref>{{cite journal | author = Kozená L | coauthors = Frantik E, Horváth M. | year = 1995 | month = May | title = Vigilance impairment after a single dose of benzodiazepines. | journal = Psychopharmacology (Berl). | volume = 119 | issue = 1 | pages = 39–45 | pmid = 7675948 | doi = 10.1007/BF02246052 }}</ref> People driving or conducting activities which require vigilance should exercise caution in using alprazolam or any other depressant. == Recreational use == [[Image:Xanax2mg.jpg|thumb|250px|[[Sandoz]] generic 2mg alprazolam tablets. Some slang names commonly used are "monkeybars" , "totempoles" , or "tombstones".]] Alprazolam, like all benzodiazepines, has the potential for abuse. Although it is not manufactured illegally{{Fact|date=June 2008}}, and its misuse and abuse is considerably less than other benzodiazepines like [[flunitrazepam]], [[nimetazepam]], and [[temazepam]], it is still often diverted to the black market, particularly in the United States where alprazolam is the most widely prescribed benzodiazepine. The state of relaxation, [[anxiolysis]], and disinhibition induced by benzodiazepines is the main reason for their illicit use. Most alprazolam abusers "are generally but not entirely limited to patients involved in a [[polydrug]] use pattern"<ref>Landry, J. ''Understanding Drugs of Abuse: The Processes of Addiction'', 1994.</ref> In fact, according to an April 2004 report by the U.S. [[SAMHSA]], "over three-quarters (78%) of benzodiazepine-related ([[emergency room]]) visits involved 2 or more drugs."<ref>[http://www.oas.samhsa.gov/DAWN/benzodiazepines.pdf 7393.14.02 DAWN tdr_Benzo<!-- Bot generated title -->]</ref>. Injection of alprazolam is considered especially dangerous by medical professionals<ref>{{cite journal | author = Eric C | coauthors = Wang, Felix S, Chew. | year = 2006 | title = MR Findings of Alprazolam Injection into the Femoral Artery with Microembolization and Rhabdomyolysis | journal = Radiology Case Reports | volume = 1 | issue = 3 | pmid = | url = http://www.radiologycasereports.net/index.php/rcr/article/viewPDFInterstitial/33/187 | format = pdf }}</ref> because, when crushed in water it will not fully dissolve (40µg/ml of H<sub>2</sub>O at pH 7, and 12 mg/mL at pH 1.2 per 1mg of alprazolam<ref>[http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00280 DrugBank: DB00404 (Alprazolam)<!-- Bot generated title -->]</ref>), 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]]; clinical testing indicates potent activity through [[insufflation]] yet some sources indicate sublingual activity is greater.<ref>[http://www.panthrax.host.sk/snort_benzos.html PanthraX-Nation - Get Addicted<!-- Bot generated title -->]</ref> Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of [[dysphoria|dysphoric]] reactions to [[psychedelic]]s 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]]s, [[DXM]], and [[MDMA]] along with the related amphetamines). It is also often used in conjunction with [[cannabis (drug)|marijuana]] or [[heroin]] to potentiate the relaxing effect. ===Patients at a high risk for abuse and dependence=== At a particularly high risk for misuse, abuse, and dependence are ''polydrug abusers'' (someone who already uses at least one substance in a recreational context). However, the following can also indicate potential problems in the future: * Patients with a history of alcohol or drug abuse and/or dependence * Patients with severe personality disorders or emotional instability * Patients with chronic pain or other physical disorders Patients from the aforementioned group should be monitored very closely during therapy for signs of abuse and development of dependence because it may cause addiction. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended, unless the net benefit to the patient outweighs the net risk. A large scale nation wide USA government study conducted by [[SAMHSA]] found that benzodiazepines in the USA are the most frequently abused pharmaceutical with 35% of drug related visits to the Emergency Department involved benzodiazepines. Benzodiazepines are more commonly abused than opiate pharmaceuticals which accounted for 32% of visits to the emergency department. No other pharmaceutical is more commonly abused than benzodiazepines. Males abuse benzodiazepines as commonly as women. Of drugs used in attempted suicide benzodiazepines are the most commonly used pharmaceutical drug with 26% of attempted suicides involving benzodiazepines. The most commonly abused benzodiazepine is however, [[alprazolam]]. Clonazepam is the 2nd most abused benzodiazepine. [[Lorazepam]] is the third most commonly abused benzodiazepine and [[diazepam]] the 4th most commonly abused benzodiazepine in the [[USA]]. Alprazolam is also commonly abused in combination with alcohol.<ref>{{cite web |url= http://dawninfo.samhsa.gov/files/DAWN2k4ED.htm |title= Drug Abuse Warning Network, 2004: National Estimates of Drug-Related Emergency Department Visits |accessdaymonth= 09 May |accessyear= 2008 |author= United States Government |authorlink= samhsa |coauthors= U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES |year= 2004 |publisher= Substance Abuse and Mental Health Services Administration}}</ref> ==Legal status== In the [[United States]], alprazolam is a prescription drug and is assigned to [[Schedule IV (US)|Schedule IV]] of the [[Controlled Substances Act]] by the [[Drug Enforcement Administration]]. Under the UK drug misuse classification system benzodiazepines are class C drugs.<ref>[http://www.statutelaw.gov.uk/content.aspx?LegType=All+Primary&PageNumber=56&NavFrom=2&parentActiveTextDocId=1367412&activetextdocid=1367464 Misuse of Drugs Act 1971 (c. 38) - Statute Law Database<!-- Bot generated title -->]</ref> Internationally, alprazolam is included under the United Nations [[Convention on Psychotropic Substances]] as Schedule IV.<ref>[http://www.incb.org/pdf/e/list/green.pdf List of psychotropic substances under international control]</ref> ==References== {{reflist}} ==External links== * [http://www.inchem.org/documents/pims/pharm/pim199.htm Inchem.org - Alprazolam] * [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a684001.html Medline Plus - Alprazolam] * [http://www.erowid.org/pharms/alprazolam Erowid.org - Alprazolam] * [http://rxlist.com/cgi/generic/alpraz.htm Rxlist.com - Alprazolam] {{Benzodiazepines}} {{Anxiolytics}} [[Category:Anxiolytics]] [[Category:Benzodiazepines]] [[Category:Hypnotics]] [[Category:Triazoles]] [[bg:Алпразолам]] [[de:Alprazolam]] [[es:Alprazolam]] [[fa:آلپرازولام]] [[fr:Alprazolam]] [[gl:Alprazolam]] [[it:Alprazolam]] [[hu:Alprazolám]] [[nl:Alprazolam]] [[ja:アルプラゾラム]] [[no:Alprazolam]] [[pl:Alprazolam]] [[pt:Alprazolam]] [[ru:Алпразолам]] [[fi:Alpratsolaami]] [[sv:Alprazolam]] [[tr:Alprazolam]] [[zh:阿普唑仑]]