Alprazolam , available under the trade name Xanax , is a powerful anxiolytic benzodiazepine, short-acting - a small sedative. It is commonly used for the treatment of anxiety disorders, especially panic disorder, but also in the treatment of generalized anxiety disorder (GAD) or social anxiety disorder. In 2010 it is the 12th most-prescribed drug in the United States. Alprazolam, like other benzodiazepines, binds to certain sites on the GABA receptor A . It has anxiolytic, sedative, hypnotic, skeletal relaxation muscle, anticonvulsant, amnestic, and antidepressant properties. Alprazolam is available for oral administration as a compressed tablet (CT), verbal disintegration tablet (ODT) and extended release tablet (XR).
The greatest reduction in generalized anxiety disorder (GAD) can take up to a week. It has been suggested that there is tolerance to the anxiolytic and antipanic effects of the drug, but not all authorities agree; However, tolerance will develop into a sedative and hypnotic effect within a few days. Symptoms of withdrawal or rebound symptoms may occur after abrupt discontinuation after a few weeks or longer than a stable dose, and may require a gradual reduction of the dose. Other risks include increased suicide rates, possibly due to disinhibition.
Alprazolam was first released by Upjohn (now part of Pfizer) in 1981. The first approved use was a panic disorder, and within two years of original marketing, Xanax became a blockbuster drug in the US. In 2010, alprazolam was the most prescribed and benzodiazepine most abused in the US. The potential for abuse among those who use it for medical reasons is controversial, with some experts suggesting that the risks are low and similar to other benzodiazepine drugs. Others claim that there is substantial risk of abuse and dependence on patients and non-medical users and that high affinity binding, high potency, short half-life elimination, and rapid onset of action can increase the potential for alprazolam abuse. Compared to a large number of prescriptions, relatively few individuals increase their doses on their own initiative or engage in drug-seeking behavior. Alprazolam is classified as controlled substance Schedule IV by the US Drug Administration (DEA).
Video Alprazolam
Medical use
Alprazolam is widely used to treat anxiety disorders, panic disorders, and nausea due to chemotherapy. Alprazolam may also be indicated for the treatment of generalized anxiety disorders, as well as for the treatment of anxiety conditions with co-morbid depression. FDA labels suggest that physicians should periodically reassess the usefulness of the drug.
Panic disorder
Alprazolam is effective in relieving anxiety and moderate to severe panic attacks. However, this is not the first-line treatment since the development of selective serotonin reuptake inhibitors. Alprazolam is no longer recommended in Australia for the treatment of panic disorder due to concerns about tolerance, dependence, and abuse. Most evidence suggests that the benefits of alprazolam in treating panic disorder lasts only 4 to 10 weeks. However, people with panic disorder have been treated openly for up to 8 months without losing any real benefits.
In the United States, alprazolam is FDA approved for the treatment of panic disorder with or without agoraphobia. Alprazolam is recommended by the World Federation of Society of Biological Psychiatry (WFSBP) for cases of medically resistant panic disorder where there is no history of tolerance or dependence.
Anxiety disorder
Anxiety associated with depression is responsive to alprazolam. Clinical studies show that its effectiveness is limited to 4 months for anxiety disorders. However, studies of the antidepressant properties of alprazolam are poor and only assess their short-term effects on depression. In one study, some high-dose and long-term alprazolam users experienced reversible depression. In the US, FDA-approved alprazolam for the management of anxiety disorder (the condition that best matches the DMA-IV-TR Diagnostic and Statistical Statistics Manual generalized anxiety disorder) or relieves anxiety symptoms. In the UK, alprazolam is recommended for short-term treatment (2-4 weeks) of severe acute anxiety.
Nausea due to chemotherapy
Alprazolam can be used in combination with other drugs for chemotherapy-induced nausea and vomiting.
Maps Alprazolam
Pregnancy and lactation
Benzodiazepines cross the placenta, enter the fetus, and are also excreted in breast milk. Chronic administration of diazepam, another benzodiazepine, to nursing mothers has been reported to cause their babies to become lethargic and lose weight.
The use of alprazolam during pregnancy is associated with congenital abnormalities, and recent trimester use may lead to 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, the sudden cessation of teratogenesis concerns has a high risk of causing extreme withdrawal symptoms and severe rebound effects of underlying mental health disorders. Spontaneous abortion can also be caused by the withdrawal of psychotropic drugs suddenly, including benzodiazepines.
Contraindications
Benzodiazepines require special precautions when used in children and individuals who are dependent on alcohol or drugs. Particular attention should be paid to pregnant or elderly persons, persons with a history of substance abuse (especially alcohol dependence), and people with comorbid psychiatric disorders. Use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with: myasthenia gravis, acute narrow angle glaucoma, severe liver deficiency (eg, cirrhosis), severe sleep apnea, existing respiratory depression, neuromuscular respiratory distress, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergies to alprazolam or other benzodiazepines, and borderline personality disorder (where it can lead to suicide and screening).
Like all central nervous system depressants, alprazolam in larger than normal doses can cause significant deterioration and increase drowsiness, especially in those unfamiliar with the effects of the drug.
Parents should be cautious in the use of alprazolam because of the increased likelihood of susceptibility to side effects, especially loss of coordination and drowsiness.
Adverse effects
Possible side effects include:
- Anterograde amnesia and concentration problems
- Ataxia, lisp talk
- Disinhibition
- Drowsiness, dizziness, dizziness, tiredness, unstable, and disturbed coordination, vertigo
- Dry mouth (rare)
- Hallucinations (rare)
- Jaundice (very rare)
- Skin rash, respiratory depression, constipation
- Idea suicide or suicide
- Urinary retention (rare)
Paradoxical reactions
Although unusual, the following paradoxical reactions have been shown to occur:
- Aggression
- Mania, agitation, hyperactive, and restless
- Rage, hostility
- Twitch and tremble
Food and drug interactions
Alprazolam is primarily metabolized through CYP3A4. Combining CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir delay liver alprazolam clearance, which can lead to accumulation and increased severity of side effects.
Imipramine and desipramine have been reported to increase an average of 31% and 20% respectively by administering alprazolam tablets simultaneously. Combined oral contraceptive pills reduce the clearance of alprazolam, which can lead to elevated plasma levels of alprazolam and accumulation.
Alcohol is one of the most common interactions; alcohol and combined alprazolam have synergistic effects with each other, which can lead to severe sedation, behavioral changes, and intoxication. The more alcohol and alprazolam, the worse the interaction. The combination of alprazolam with kava ingredients can lead to the development of semi-coma conditions. Plants in the genus Hypericum (including St. John's wort) may otherwise decrease plasma levels of alprazolam and reduce their therapeutic effects.
Overdose
Overdose of alprazolam can be mild to severe depending on the quantity ingested and if other drugs are taken in combination.
Overdose of Alprazolam causes excessive central nervous system (CNS) depression and may include one or more of the following symptoms:
- Coma and death if alprazolam is combined with other substances.
- Faint
- Hypotension (low blood pressure)
- Hypoventilation (shallow breathing)
- Impaired motor function
- Dizzy
- Residual interruption
- Impaired or absent reflexes
- Muscle weakness
- Orthostatic hypotension (stupor when standing too fast)
- Somnolen (drowsy)
Dependence and tethering
Alprazolam, like other benzodiazepines, binds to certain sites on the GABA recipe A (gamma-aminobutyric acid). When bound to these sites, referred to as benzodiazepine receptors, it modulates the effects of GABA receptors A and, thus, of GABAergic neurons. Long-term use causes adaptive changes in benzodiazepine receptors, making them less sensitive to stimuli and thus making less powerful drugs.
Withdrawal and rebounding symptoms generally occur and require a gradual reduction of doses to minimize withdrawal effects when stopping.
Not all withdrawal effects are evidence of true dependence or withdrawal. The return of symptoms such as anxiety may simply indicate that the drug has the expected anti-anxiety effect and that, in the absence of the drug, the symptoms have returned to pre-treatment levels. If symptoms are more severe or frequent, the person may experience a rebounding effect due to drug elimination. One of these can happen without a person who is totally dependent on the drug.
Alprazolam and other benzodiazepines can also lead to the development of physical dependence, tolerance, and withdrawal symptoms of benzodiazepines during rapid dose reduction or treatment interruption after long-term treatment. There is a higher likelihood of a withdrawal reaction if the drug is given in a higher dose than recommended, or if one stops taking the drug altogether without slowly allowing the body to adjust to a lower dose regimen.
In 1992, Romach and colleagues reported that dose escalation was not a characteristic of long-term alprazolam users, and that the majority of long-term alprazolam users changed the initial pattern of regular use to one of the symptoms controls only when necessary.
Some common symptoms of alprazolam termination include malaise, weakness, insomnia, tachycardia, dizziness, and dizziness.
Those who consume more than 4 mg per day have the potential for increased dependence. These drugs may cause withdrawal symptoms of sudden withdrawal or rapid tapering, which in some cases have been known to cause seizures, as well as delirium marked similar to those produced by tropicolinolinic Dulpha (scopolamine and atropine) alkaloids. Cessation of this drug can also cause a reaction called rebound anxiety .
In a 1983 study, only 5% of patients who suddenly stopped taking long-term benzodiazepines after less than 8 months showed withdrawal symptoms, but 43% of those who had drunk them for more than 8 months. With alprazolam - benzodiazepine short-acting - taken for 8 weeks, 65% of patients experienced significant rebound anxiety. To some degree, the older benzodiazepines are self-tapered.
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 severity of benzodiazepine withdrawal symptoms during alprazolam dose reduction include: dose used, duration of use, frequency of dosing, individual personality characteristics, prior use of cross-linked/cross-tolerant drugs (alcohol or drugs hypnotic tranquilizers), the use of drugs that depend on cross-current tolerance, the use of short-acting benzodiazepines, high potency, and discontinuation methods.
Detection in body fluids
Alprazolam can be quantified in blood or plasma to confirm the diagnosis of poisoning in hospitalized patients, provide evidence in a driving disorder, or to assist in investigation of medicolegal death. Blood plasma or plasma alprazolam concentrations are usually in the range of 10-100 μg/L in people receiving therapeutic drugs, 100-300 μg/L in those arrested for driving disorders, and 300-2000 μg/L in victims of acute overdose. Most commercial immunoassays for the benzodiazepine drug class react with crosslinked alprazolam, but confirmation and quantization are usually performed using chromatographic techniques.
Pharmacology
Action mechanism
Alprazolam is classified as a highly capable triazolobenzodiazepine: benzodiazepine with a triazole ring attached to its structure. As benzodiazepine, alprazolam produces a variety of therapeutic effects and side effects by binding to the benzodiazepine receptor site at GABA A receptors and modulating its function; GABA receptors are the most productive inhibitory receptors in the brain. The chemical system and GABA receptors mediate the inhibitory or calming effects of alprazolam on the nervous system. The GABA A receptor consists of 5 subunits of possibly 19, and the GABA receptor A consisting of a combination of different subunits having different properties, different locations within the brain. , and, importantly, different activities related to benzodiazepines. Alprazolam and other triazolobenzodiazepines such as triazolam which have triazole rings attached to their structure appear to have antidepressant properties, because their structures resemble tricyclic antidepressants, which also have a ring. Alprazolam causes suppression of hypothalamic-pituitary axis suppression. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxants, hypnotics and amnesia; however, it is used primarily as anxiolytic.
Administration of alprazolam, compared with lorazepam, has been shown to lead to a statistically significant increase in D1 extracellular D1 and D2 concentrations in the striatum.
Pharmacokinetics
Alprazolam is taken orally, and is well absorbed - 80% of alprazolam binds proteins in serum (the majority of which bind albumin). Peak concentration of alprazolam after one to two hours.
Alprazolam is metabolized in the liver, mostly by the enzyme cytochrome P450 3A4 (CYP3A4). Two main metabolites are generated: 4-hydroxyalprazolam and? -hydroxyalprazolam, as well as inactive benzophenone. Low concentrations and low potency of 4-hydroxyalprazolam and? -hydroxyalprazolam shows that they have little or no contribution to the effects of alprazolam.
Metabolites, as well as some non-metabolized alprazolam, are filtered by the kidneys and excreted in the urine.
The shape of alprazolam
Regular release of Alprazolam and oral disintegrated tablets are available as 0.25 mg, 0.5 mg, 1 mg, and 2 mg tablets, while extended release tablets are available as 0.5 mg, 1 mg, 2 mg, and 3 mg. Oral solution of Alprazolam is available as 0.5 mg/5 mL and as 1 mg/1 mL oral solution. The active ingredients in alprazolam tablets and their solutions include microcrystalline cellulose, corn starch, sodium docusate, povidone, sodium starch glycolate, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, and sodium benzoate. In addition, 0.25 mg tablet contains D & amp; C Yellow No. 10 and 0.5 mg tablet containing FD & amp; C Yellow No. 6 and D & amp; C Yellow No. 10.
Society and culture
Patent
Alprazolam is included in U.S. Patent 3,987,052 , filed on 29 October 1969, granted on October 19, 1976, and ended in September 1993.
Use of recreation
There is a risk of abuse and dependence on patients and users of non-medical alprazolam; high affinity alprazolam binder, high potency, and rapid onset increase the potential for abuse. Physical dependence and alprazolam withdrawal syndrome also add to its addictive properties. In a small subgroup of individuals who increase their dosage there is usually a history of alcohol or other substance use disorders. Nonetheless, most of the prescribed alprazolam users do not use their drugs on a recreational basis, and long-term use of benzodiazepines is generally uncorrelated to the need for dose escalation. However, based on the US findings of the Treatment Episode Data Set (TEDS), the annual compilation of patient characteristics in substance abuse treatment facilities in the United States, acceptance for "major sedatives" (including, but not limited to, benzodiazepine) drug use increased 79% 1992 to 2002, suggesting that abuse of benzodiazepines may increase. In 2011, The New York Times reported, "The Centers for Disease Control and Prevention last year reported an 89 percent increase in national emergency room visits linked to the use of benzodiazepine nonmedisation between 2004 and 2008."
Alprazolam is one of the most commonly prescribed and abused benzodiazepines in the United States. Massive national ASS study conducted by SAMHSA found that, in the US, benzodiazepines are the most commonly used drugs due to their widespread availability, accounting for 35% of all hospital-related visits to emergency hospitals and care facilities urgent. Men and women alike tend to use benzodiazepines in recreation. The report found that alprazolam is the most common benzodiazepine for recreational use, followed by clonazepam, lorazepam, and diazepam. The number of emergency room visits due to benzodiazepines increased 36% between 2004 and 2006.
Regarding the significant increase detected, it is important to consider that the number of drugs issued for valid therapeutic use may increase over time, and DAWN estimates are not adjusted to account for the increase. Neither did the estimates of DAWN take into account population increases or in the use of ED between 2004 and 2006.
Those who are at extreme risk for abuse and dependence are people with a history of alcoholism or drug abuse and/or dependence and people with personality disorder thresholds.
Alprazolam, along with other benzodiazepines, is often used with other recreational medicines. This use includes help to relieve panic or sadness from dysphoric reactions to psychedelic drugs, such as LSD, and drug-induced agitation and insomnia in the "comedy" stage of stimulant use, such as amphetamine, cocaine. , and MDMA allows sleep. Alprazolam can also be used with other depressant drugs, such as ethanol, heroin, and other opioids, in an attempt to improve their psychological effects. Alprazolam can be used in conjunction with cannabis, with users citing the synergistic effects achieved after consuming the combination.
The use of powerful drug-resistant depressant drugs is the highest health problem because of an increased likelihood of having an overdose, which can lead to fatal respiratory depression.
A 1990 study claimed that diazepam has a higher potential of abuse relative to other benzodiazepines, and that some data suggest that alprazolam and lorazepam resemble diazepam in this regard.
Anecdotal injection of alprazolam has been reported, causing harmful damage to blood vessels, closure of blood vessels (embolization) and decay of muscle tissue (rhabdomyolysis). Alprazolam is not very soluble in water - when it is destroyed in water it is not completely soluble (40 Âμg/ml H 2 O at pH 7). There are also anecdotal reports of alprazolam being snorted. Due to its low dose weight, alprazolam, in one case, is distributed on ink paper in a manner similar to LSD.
Popular culture
The term slang for alprazolam varies from one place to another. Some of the more common terms are shortened versions of the "Xanax" trade names, such as Xannies (or Xanies) and phonetic equivalents of Zannies; references to their drug classes, such as benzos or downers; or comment on their shape or color (most common straight, hollow or oval-shaped tablets): bar, staircase, Xanbars, Z-bar, football, board, pole, blues, or blue ball.
Availability
Alprazolam is available in English-speaking countries with the following brand names:
- Alprax, Alprocontin, Alzam, Alzolam, Anzilum, Apo-Alpraz, Helex, Kalma, Mylan-Alprazolam, Niravam, Novo-Alprazol, Nu-Alpraz, Pacil, Restyl, Tranax, Trika, Xycalm, Xanax, Xanor, Zolam, Zopax.
In December 2013, in anticipation of rescheduling alprazolam to Schedule 8 in Australia - Pfizer Australia announced that it will stop the Xanax brand in Australia because it is no longer commercially viable.
Legal status
Alprazolam has varying legal status depending on the jurisdiction:
- In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substance Act by the Drug Eradication Administration.
- Under the drug abuse classification system in the UK, benzodiazepines are class C drugs (Schedule 4). Note that in the UK, alprazolam is not available in the NHS and can only be obtained by private recipes.
- In Ireland, alprazolam is a drug Schedule 4.
- In Sweden, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drug Act (1968).
- In the Netherlands, alprazolam is the 2nd List of the Opium Law and available for prescription.
- In Germany, alprazolam can be prescribed normally in doses up to 1 mg. A higher dose is scheduled as an Anlage III drug and requires a special prescription form.
- In Australia, alprazolam originally is drug Schedule 4 (Recipe Only); however, since February 2014, this has become a remedy Schedule 8, which makes it more in line with stricter prescription requirements.
Internationally, alprazolam belongs to the UN Convention on Psychotropic Substances as Schedule IV.
References
External links
- US. National Drug Library: Drug Information Portal - Alprazolam
Source of the article : Wikipedia
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