与地西泮相似，但较轻微。少数患者有倦乏、头晕、口干、恶心、便秘、视力模糊、精神不集中等。久用后停药有戒断症状,应避免长期使用。
Xanax(Alprazolam)
Alprazolam, sold under the trade name Xanax among others, is a short-acting benzodiazepine.[4] It is most commonly used in short term management of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD).[5] Other uses include chemotherapy-induced nausea, together with other treatments.[6] GAD improvement occurs generally within a week.[7][8] Alprazolam is available by mouth.[6]
Common side effects include sleepiness, depression, headaches, feeling tired, dry mouth, and memory problems.[6] Some of the sedation and tiredness may improve within a few days.[9] Due to concerns about misuse, some do not recommend alprazolam as an initial treatment for panic disorder.[10] Withdrawal or rebound symptoms may occur if use is suddenly decreased.[6] Other rare risks include suicide, possibly due to loss of inhibition.[11]Gradually decreasing the dose over weeks or months may be required.[7] Alprazolam, like other benzodiazepines, acts through the GABAA receptor.[6]
Alprazolam was patented in 1971 and approved for medical use in the United States in 1981.[6][12] Overall, in 2010, it was the 12th most prescribed medicine in the United States.[13] Alprazolam is a Schedule IV controlled substance and is a common drug of abuse.[14][1] It is available as a generic medication.[13] The wholesale cost in the United States is less than 0.03 USD per dose as of 2018.[15] In 2016, it was the 19th most prescribed medication in the United States, with more than 27 million prescriptions.[16]
Medical uses
Alprazolam is mostly used in short term management of anxiety disorders, panic disorders, and nausea due to chemotherapy.[6] Alprazolam may also be indicated for the treatment of generalized anxiety disorder, as well as for the treatment of anxiety conditions with co-morbid depression.[3] The FDA label advises that the physician should periodically reassess the usefulness of the drug.[17]
Panic disorder
Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks.[17]However, it is not a 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 regarding tolerance, dependence, and abuse.[10] Most evidence shows that the benefits of alprazolam in treating panic disorder last only 4 to 10 weeks. However, people with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit.[17][3]
In the United States, alprazolam is FDA-approved for the treatment of panic disorder with or without agoraphobia.[17] 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.[18]
Anxiety disorders
Anxiety associated with depression is responsive to alprazolam. Clinical studies have shown that the effectiveness is limited to 4 months for anxiety disorders.[17] However, the research into antidepressant properties of alprazolam is poor and has only assessed its short-term effects against depression.[19] In one study, some long term, high-dosage users of alprazolam developed reversible depression.[20] 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-IV-TR diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. In the UK, alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety.[3][21][22]
Nausea due to chemotherapy
Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.[6]
Contraindications
Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly people, people with substance abuse history (particularly alcohol dependence), and people with comorbidpsychiatric disorders.[23] The use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with: myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies (e.g., cirrhosis), severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergy to alprazolam or other benzodiazepines, and borderline personality disorder (where it may induce suicidality and dyscontrol).[22][24][25]
Like all central nervous system depressants, alprazolam in larger-than-normal doses can cause significant deterioration in alertness and increase drowsiness, especially in those unaccustomed to the drug's effects.[26]
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.[27]
Adverse effects
Sedative drugs, including alprazolam, have been associated with an increased risk of death.[28]
Possible side effects include:
§ Anterograde amnesia[29] and concentration problems
§ Ataxia, slurred speech[30]
§ Disinhibition[31]
§ Drowsiness, dizziness, lightheadedness, fatigue, unsteadiness, and impaired coordination, vertigo[32][33]
§ Dry mouth (infrequent)[34]
§ Hallucinations (rare)[35]
§ Jaundice (very rare)[36]
§ Skin rash, respiratory depression, constipation[32][33]
§ Suicidal ideation or suicide[11]
§ Urinary retention (infrequent)[35]
Paradoxical reactions
Although unusual, the following paradoxical reactions have been shown to occur:
§ Aggression[37]
§ Mania, agitation, hyperactivity, and restlessness[38][39][40]
§ Rage, hostility[31]
§ Twitches and tremor[41]
Food and drug interactions
Alprazolam is primarily metabolized via CYP3A4.[42] Combining CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir delay the hepatic clearance of alprazolam, which may result in its accumulation[43] and increased severity of its side effects.[44][45]
Imipramine and desipramine have been reported increase an average of 31% and 20% respectively by the concomitant administration of alprazolam tablets.[46] Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.[47]
Alcohol is one of the most common interactions; alcohol and 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.[31]Combination of alprazolam with the herb kava can result in the development of a semi-comatose state.[48] Plants in the genus Hypericum (including St. John's wort) conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.[49][50][51]
Pregnancy and breastfeeding
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 infants to become lethargic and to lose weight.[27][52]
The use of alprazolam during pregnancy is associated with congenital abnormalities,[3][53] and 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.[54][55] 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.[56]
Overdose
Overdoses of alprazolam can be mild to severe depending on the quantity ingested and if other drugs are taken in combination.[57]
Alprazolam overdoses cause excess central nervous system (CNS) depression and may include one or more of the following symptoms:[35]
§ Coma and death if alprazolam is combined with other substances.
§ Fainting
§ Hypotension (low blood pressure)
§ Hypoventilation (shallow breathing)
§ Impaired motor functions
· Dizziness
· Impaired balance
· Impaired or absent reflexes
· Muscle weakness
§ Orthostatic hypotension (fainting while standing up too quickly)
§ Somnolence (drowsiness)
Mechanism of action
Alprazolam is classed as a high-potency triazolobenzodiazepine:[78][79] a benzodiazepine with a triazole ring attached to its structure. As a benzodiazepine, alprazolam produces a variety of therapeutic and adverse effects by binding to the GABAA benzodiazepine receptor site and modulating its function; GABA receptors are 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. Binding of alprazolam to the GABAA receptor, a chloride ion channel, enhances the effects of GABA, a neurotransmitter. When GABA binds the GABAA receptor the channel opens and chloride enters the cell which makes it more resistant to depolarisation. Therefore, alprazolam has a depressant effect on synaptic transmission to reduce anxiety.[80][81]
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. Alprazolam and other triazolobenzodiazepines such as triazolam that have a triazole ring fused to their diazepine ring appear to have antidepressant properties.[29][82] This is perhaps due to the similarities shared with tricyclic antidepressants, as they have two benzene rings fused to a diazepine ring. 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[83] and amnesic; however, it is used mainly as an anxiolytic.
Giving alprazolam, as compared to lorazepam, has been demonstrated to elicit a statistically significant increase in extracellular dopamine D1and D2 concentrations in the striatum.[84][85]
