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Алпразолам

Алпразолам, лекарственное средство, анксиолитик (противотревожное средство), производное бензодиазепина средней продолжительности действия, которое используется для лечения тревожных расстройств, панических атак.

По химическому строению близок к триазоламу, отличается отсутствием атома Cl при фениле в положении 6. У А. менее выражен снотворный эффект. Применяется преимущественно для кратковременного снятия чувства беспокойства, страха, тревоги. 

Абсорбция после приема внутрь быстрая и полная. TCmax — 1-2 ч. Связь с белками плазмы — 80 %. Может проходить через плаценту,гемато-энцефалический барьер, проникать в грудное молоко. Css в плазме обычно достигается в течение нескольких (2-3) дней. Метаболизируется в печени до малоактивных или неактивных метаболитов. В метаболизме препарата участвуют изоферменты CYP3A4,CYP3A5 и CYP3A7. T1/2 — 11-16 ч. Выводится преимущественно почками в виде соединений с глюкуроновой кислотой. Накопление при повторном назначении — минимальное (относится к бензодиазепинам со средним T1/2), выведение после прекращения лечения — быстрое.

Показания: тревожные состояния и неврозы с тревогой, напряжением, беспокойством, раздражительностью, ухудшением сна, соматическими нарушениями. Панические расстройства (лечение). Тремор (старческий, эссенциальный). Бессонница.

Противопоказания: гиперчувствительность, кома, шок, миастения, закрытоугольная глаукома (острый приступ или предрасположенность), острые отравленияалкоголем (с ослаблением жизненно важных функций), наркотическими анальгетиками, снотворными и психоактивными лекарственными средствами; тяжелая ХОБЛ (прогрессирование степени дыхательной недостаточности), острая дыхательная недостаточность; тяжелая депрессия (могут проявляться суицидальные наклонности); беременность (особенно I триместр), период лактации, возраст до 18 лет (безопасность и эффективность не определены).

C осторожностью: печеночная недостаточность, хроническая почечная недостаточность, церебральные и спинальные атаксии, лекарственная зависимость ванамнезе, склонность к злоупотреблению психоактивными лекарственными средствами, гиперкинезы, органические заболевания головного мозга, психоз (возможны парадоксальные реакции), гипопротеинемия, ночные апноэ (установленное или предполагаемое), пожилой возраст.

Режим дозирования: внутрь, 2-3 раза в день независимо от приема пищи. Дозы подбирают в зависимости от выраженности синдрома, индивидуальной чувствительности больного и его реакции на препарат. Начинают с минимальных доз — по 0.5 мг 3 раза в сутки, суточная доза должна достигать 3-6 мг, высшая суточная доза — 10 мг. Длительность назначения алпразолама — до 3 мес. При необходимости прекращения терапии дозу снижают постепенно на 0.5 мг каждые 3 дня.

Побочные эффекты

Со стороны нервной системы

В начале лечения (особенно у пожилых больных) — сонливость, чувство усталости, головокружение, снижение способности к концентрации внимания, атаксия, дезориентация, замедление психических и двигательных реакций; редко — головная боль, эйфория, депрессия, тремор, снижение памяти, нарушения координации движений, подавленность настроения, спутанность сознания, дистонические экстрапирамидные реакции (неконтролируемые движения, в том числе глаз), слабость, миастения, дизартрия; крайне редко — парадоксальные реакции (агрессивные вспышки, спутанность сознания, психомоторное возбуждение, страх, суицидальная наклонность, мышечный спазм,галлюцинации, возбуждение, раздражительность, тревожность, бессонница).

Со стороны органов кроветворения

Лейкопения, нейтропения, агранулоцитоз (озноб, гипертермия, боль в горле, чрезмерная утомляемость или слабость), анемия, тромбоцитопения.

Со стороны пищеварительной системы

Сухость во рту или слюнотечение, изжога, тошнота, рвота, снижение аппетита, запоры или диарея; нарушение функции печени, повышение активности «печеночных» трансаминаз и ЩФ,желтуха.

Со стороны мочеполовой системы

Недержание мочи, задержка мочи, нарушение функции почек, снижение или повышение либидо, дисменорея.

Аллергические реакции: кожная сыпь, зуд.

Влияние на плод: тератогенность (особенно I триместр), угнетение центральной нервной системы, нарушение дыхания и подавление сосательного рефлекса у новорожденных, матери которых применяли препарат.

Прочие: привыкание, лекарственная зависимость; снижение артериального давления; редко — нарушение зрения (диплопия), снижение массы тела, тахикардия. При резком снижении дозы или прекращении приема — синдром отмены (раздражительность, нервозность, нарушения сна, дисфория, спазм гладких мышц внутренних органов и скелетной мускулатуры,деперсонализация, усиление потоотделения, депрессия, тошнота, рвота, тремор, расстройства восприятия, в том числе гиперакузия, парестезии, светобоязнь; тахикардия, судороги, редко — острый психоз).

Передозировка: сонливость, спутанность сознания, снижение рефлексов, нистагм, тремор, брадикардия, одышка или затрудненное дыхание, снижение артериального давления, кома.

Лечение: промывание желудка, прием активированного угля. Симптоматическая терапия (поддержание дыхания и артериального давления), введение флумазенила (в условиях стационара).Гемодиализ малоэффективен. 

В процессе лечения А. больным категорически запрещается употребление этанола. Эффективность и безопасность применения препарата у пациентов моложе 18 лет не установлена. При почечной/печеночной недостаточности и длительном лечении необходим контроль за картиной периферической крови и «печеночными» ферментами. Пациенты, не принимавшие ранее психоактивные лекарственные средства, «отвечают» на препарат в более низких дозах по сравнению с больными, принимавшими антидепрессанты, анксиолитики или страдающими алкоголизмом. При эндогенных депрессиях алпразолам можно применять в комбинации с антидепрессантами. При применении алпразолама больными депрессией отмечены случаи развития гипоманиакального и маниакального состояния. Подобно другим бензодиазепинам, алпразолам обладает способностью вызывать лекарственную зависимость при длительном приеме в больших дозах (более 4 мг/сут). При внезапном прекращении приема алпразолама может отмечаться синдром «отмены» (депрессии, раздражительность, бессонница, повышенное потоотделение и др.), особенно при длительном приеме (более 8-12 нед). При возникновении у больных таких необычных реакций, как повышенная агрессивность, острые состояния возбуждения, чувство страха, мысли о самоубийстве, галлюцинации, усиление мышечных судорог, трудное засыпание, поверхностный сон, лечение следует прекратить. В период беременности применяют только в исключительных случаях и только по «жизненным» показаниям. Оказывает токсическое действие на плод и увеличивает риск развития врожденных пороков при применении в I триместре беременности. Прием терапевтических доз в более поздние сроки беременности может вызвать угнетение центральной нервной системы новорожденного. Постоянное применение во время беременности может приводить к физической зависимости с развитием синдрома «отмены» у новорожденного. Дети, особенно в младшем возрасте, очень чувствительны к угнетающему центральную нервную систему действию бензодиазепинов. Использование непосредственно перед родами или во время родов может вызывать у новорожденного угнетение дыхания, снижение мышечного тонуса, гипотонию, гипотермию и слабый акт сосания (синдром «вялого ребенка»). В период лечения необходимо соблюдать осторожность при вождении автотранспорта и занятии другими потенциально опасными видами деятельности, требующими повышенной концентрации внимания и быстроты психомоторных реакций. 

Отмечается взаимное усиление эффекта при одновременном назначении антипсихотических (нейролептических), противоэпилептических или снотворных лекарственных средств, а также центральных миорелаксантов, наркотических анальгетиков, этанола и лекарственных средств для общей анестезии. Ингибиторы микросомального окисления ферментов печени повышают, а индукторы снижают концентрацию алпразолама в плазме (возможно изменение эффективности алпразолама). Алпразолам может усиливать выраженность снижения артериального давления на фоне гипотензивных лекарственных средств. При одновременном назначении с клозапином возможно усиление угнетения дыхания. Снижает эффективность леводопы у больныхпаркинсонизмом. Может повышать токсичность зидовудина. 

Список №1 сильнодействующих веществ ПККН. Хранить при температуре не выше 30°С.


Alprazolam  /ælˈpræzəlæm/ (trade name Xanax, available among other generic names) is a short-acting anxiolytic of the benzodiazepine class ofpsychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor. Alprazolam is commonly used and FDA approved for the treatment of panic disorder, and anxiety disorders, such as generalized anxiety disorder (GAD) orsocial anxiety disorder (SAD). Alprazolam is available for oral administration in compressed tablet (CT) and extended-release capsule (XR) formulations. Alprazolam possesses anxiolytic, sedative, hypnotic, skeletal muscle relaxant, anticonvulsant, and amnestic properties. 

Alprazolam has a fast onset of action and symptomatic relief. 90% of peak benefits are achieved within the first hour of using either preparation forpanic disorder, and full peak benefits are achieved in 1.5 and 1.6 hours respectively. Peak benefits achieved for generalized anxiety disorder(GAD) may take up to a week.  Tolerance does not appear to develop to the anxiolytic effects  but may develop to the sedative effects within a couple of days.  Withdrawal symptoms or rebound symptoms may occur after ceasing treatment abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. 

Alprazolam is the most prescribed,  and the most misused benzodiazepine on the U.S. retail market.  The potential for abuse is low   and is similar to that of other benzodiazepine drugs.  Compared to the large number of prescriptions, relatively few individuals increase their dose on their own initiative or engage in drug-seeking behavior.  Alprazolam is classified as a schedule C IV controlled substance by the U.S. Drug Enforcement Agency (DEA). 

Alprazolam is primarily used to treat anxiety disorders, panic disorders, and nausea due to chemotherapy. The FDA label advises that the physician should periodically reassess the usefulness of the drug.

In the US alprazolam is FDA-approved for the treatment of panic disorder with or without agoraphobia. Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks. Systematic clinical studies of effectiveness in treating panic disorder have been limited to 4 to 10 weeks. However, patients with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit. 

Alprazolam is recommended by the World Federation of Societies of Biological Psychiatry (WFSBP) for treatment resistant cases of panic disorder where there is no history of tolerance or dependence, as of 2002. 

In the US alprazolam is FDA-approved 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. Anxiety associated with depression is responsive to alprazolam. Demonstrations of the effectiveness by systematic clinical study are limited to 4 months duration for anxiety disorder. 

In the UK, alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety. 

Long term users of alprazolam may develop depression.  

Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.  

Benzodiazepines cross the placenta, enter into the fetus and are also excreted with breast milk. The use of benzodiazepines during pregnancy orlactation has potential risks. The use of alprazolam in pregnancy is believed to be associated with congenital abnormalities. Diazepam andchlordiazepoxide have a better safety profile in pregnancy than alprazolam.

Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam.  Use in the last trimester may cause fetal drug dependence and withdrawal symptoms in the post-natal period  as well as neonatal flaccidity and respiratory problems. However, in long-term users of benzodiazepines abrupt discontinuation due to concerns of teratogenesis has a high risk of causing extreme withdrawal symptoms and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications including benzodiazepines. 

Benzodiazepines, including alprazolam, are known to be excreted in human milk.  Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.  

Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly patients, patients with substance abuse history, particularly alcohol dependence and patients with comorbid psychiatric disorders.  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). 

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.  People driving or conducting activities that require vigilance should exercise caution in using alprazolam or any other depressant.

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.

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: yellowingof the skin or eyes. Other side-effects that may occur are as follows:

  • Drowsiness, dizziness, lightheadedness, fatigue, unsteadiness and impaired coordination, vertigo 

  • Skin rash, respiratory depression, constipation 

  • Disinhibition 

  • Suicidal ideation (rare) 

  • Urinary retention (infrequent) 

  • Hallucinations (rare) 

  • Ataxia, slurred speech 

  • Anterograde amnesia  and concentration problems

  • Change in libido 

  • Dry mouth (infrequent) 

  • Jaundice (very rare)  

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

  • Twitches and tremor 

  • Aggression 

  • Rage, hostility 

  • Mania, agitation, hyperactivity and restlessness  

Alprazolam is primarily metabolised via CYP3A4. Combining CYP3A4 inhibitors with alprazolam can lead to profound sedating effects. 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. 

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. Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation. 

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. Combination of alprazolam with the herb kava can result in the development of a semi-comatose state.  Hypericum conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.

Overdoses of alprazolam can be mild to severe depending on how much of the drug is taken and any other drugs that have been taken.[ 

Alprazolam overdoses cause excess central nervous system (CNS) depression and may include one or more of the following symptoms: 

  • Somnolence (sleepy state)

  • Hypotension (low blood pressure)

  • Hypoventilation (shallow breathing)

  • Impaired motor functions

    • Dizziness

    • Impaired balance

    • Muscle weakness

    • Impaired or absent reflexes

  • Fainting

  • Coma

  • Death (very rare)

In a study of deaths in Palm Beach County where the drug alprazolam was detected, approx. 50% of cases were attributed to poly-drug use (the combined toxicity of two or more drugs). The majority of these cases included either cocaine or methadone. Alprazolam alone caused only 1% of the deaths. These results indicate alprazolam has a very low incidence of causing death when taken alone.

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, GABAergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and less powerful in their effects. 

Withdrawal and rebound symptoms occur commonly and necessitate a gradual reduction in dosage to minimize withdrawal effects when discontinuing.

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. 

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.  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. 

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. 

Some common symptoms of alprazolam discontinuation include malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness. 

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. 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. 

Delirium and seizures have been anecdotally reported in the medical literature from abrupt alprazolam discontinuation. 

In a 1983 study of patients who had taken long-acting benzodiazepines, e.g., clorazepate, for extended periods, the medications were stopped abruptly. Only 5% of patients who had been taking the drug for less than 8 months demonstrated withdrawal symptoms, but 43% of those who had been taking them for more than 8 months did. 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. 

The benzodiazepines diazepam (Valium) and oxazepam (Serepax) have been found to produce fewer withdrawal reactions than alprazolam (Xanax), temazepam (Restoril/Normison), 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/-tolerant drugs, use of other short-acting, high-potency benzodiazepines,  and method of discontinuation.

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.  

Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine, namely a benzodiazepine with a triazole ring attached to its structure. Benzodiazepines produce a variety of therapeutic and adverse effects by binding to the benzodiazepine receptor 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 of 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, importantly, different activities with regard to benzodiazepines. Benzodiazepines and in particular alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic  and amnesic.  

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 metabolitesare 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.  

Alprazolam is a chemical analog of triazolam that differs by the absence of a chlorine atom in the o-position of the 6-phenyl ring. The same scheme that was used to make triazolam can be used to make alprazolam, with the exception that it begins with 2-amino-5-chlorobenzophenone.  However, a non-standard way of making alprazolam has been suggested, which comes from 2,6-dichloro-4-phenylquinoline, the reaction of which with hydrazine gives 6-chloro-2-hydrazino-4-phenylquinoline. Boiling this with triethyl orthoacetate in xylene leads to the heterocyclization into a triazolederivative. The resulting product undergoes oxidative cleavage using sodium periodate and ruthenium dioxide in an acetone–water system to give 2-[4-(3′-methyl-1,2,4-triazolo)]-5-chlorobenzophenone. Oxymethylation of the last using formaldehyde and subsequent substitution of the resulting hydroxyl group by phosphorus tribromide,gives 2-[4-(3′-methyl-5′-bromomethyl-1,2,4-triazolo)]-5-chlorobenzophenone. Substitution of the bromine atom with an amino group using ammonia and the spontaneous, intramolecular heterocyclization following that reaction gives alprazolam.

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. 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.[clarification needed] 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 the first group of patients treated by alprazolam as so impressed by its action that the company knew outright that the 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.

Soon after its introduction a number of case reports were published in the medical literature of severe withdrawal symptoms, including psychoses, seizures and intense rebound anxiety, upon discontinuation of alprazolam.  

Most prescribed alprazolam users do not misuse their medication, and the long-term use of benzodiazepines doesn't generally collaborate with the need for dose escalation. However, based on US findings from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance abuse treatment facilities in the United States, admissions due to "primary tranquilizer" (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002, suggesting that misuse of benzodiazepines may be on the rise.

Alprazolam is one of the most commonly prescribed and misused benzodiazepines in the United States. A large-scale nationwide U.S. government study conducted by SAMHSA found that, in the U.S., benzodiazepines are recreationally the most frequently used pharmaceuticals due to their widespread availability, accounting for 35% of all drug-related visits to hospital emergency and urgent care facilities. 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. 

At a particularly high risk for misuse and dependence are people with a history of alcoholism or drug abuse and/or dependence and people with borderline personality disorder. 

Alprazolam, along with other benzodiazepines, is often used with other recreational drugs. These uses include aids to relieve the panic or distress of dysphoric ("bad trip") reactions to psychedelic drugs, such as LSD, and is often used in the "comedown" stages of stimulant use, such as amphetamine, in order to help relieve drug-induced agitation and insomnia, allowing sleep. Alprazolam may also be used in conjunction with other depressant drugs, such as alcohol, marijuana, heroin or other opiates, in an attempt to enhance the psychological effect of these drugs.

The poly-drug use of powerful depressant drugs poses the highest level of health concerns due to a significant increase in the likelihood of experiencing an overdose which may result in fatal respiratory depression. 

A 1990 study claimed that diazepam has a higher misuse potential relative to other benzodiazepines, and that some data suggests that alprazolam and lorazepam resemble diazepam in this respect. 

Anecdotally injection of alprazolam has been reported, causing dangerous damage to blood vessels, closure of blood vessels (embolization) and decay of muscle tissue (rhabdomyolysis). Alprazolam is practically not soluble in water, when crushed in water it will not fully dissolve (40 µg/ml of H2O at pH 7). There have also been anecdotal reports of alprazolam being snorted. 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.  

Alprazolam instant release (IR) is available in 0.125 mg, 0.25 mg, 0.5 mg, 1 mg and 2 mg strength regular and orally disintegrating tablets.  Alprazolam Extended Release (XR) is available in 0.5 mg, 1 mg, 2 mg, and 3 mg strength oral.

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

  • Alprax, Alprocontin, Anzilum, Apo-Alpraz, Kalma, Niravam, Novo-Alprazol, Nu-Alpraz, Pacyl, Restyl, Tranax, Xycalm, Xanax, Zolam 

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. Under the UK drug misuse classification system benzodiazepines are class C drugs (Schedule 4).  In the UK, alprazolam is not available on the NHS and can only be obtained on private prescription. Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.  In Ireland, alprazolam is a Schedule 4 medicine. In Sweden, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).  In the Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription.

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