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Alprazolam pharmachologic effect

Alprazolam - anxiolytic agent with some antidepressant, hypnotic and anticonvulsant effect. Alprazolam increases the inhibitory effect of gamma-aminobutyric acid in the central nervous system, increases the sensitivity of GABA receptors to this mediator by stimulating the benzodiazepine receptor supramolecular complex prescription GABA-benzodiazepine-hlorionofor. When receiving alprazolam patients have muscle relaxation. Alprazolam has some anticonvulsant activity

The drug Alprazolam has a mild sedative effect, in particular, makes it easier to fall asleep, it increases the duration of sleep, and also leads to a decrease in the number of nighttime awakenings. Hypnotic action alprazolam mechanism is based on its ability to inhibit cells in the reticular formation of the brain stem, and also reduce the impact of autonomic, motor and emotional stimuli affecting the process of falling asleep.

When receiving the drug Alprazolam in patients noted a decrease in the symptoms of anxiety and fear, as well as the reduction of emotional stress. Alprazolam is almost no effect on the cardiovascular and respiratory system in healthy patients.

Mode of action Alprazolam - anxiolytic, sedative, muscle relaxant, central. By binding to benzodiazepine and GABAergic receptors causes inhibition of the limbic system, thalamus, hypothalamus, polysynaptic spinal reflexes. After intake of rapidly absorbed from the gastrointestinal tract. Cmax achieved within 1-2 h. Plasma protein binding is 80%. It passes through GEB and placental barrier, enters the breast milk. It is metabolized in the liver. T1 / 2 -. 16 hours is derived mainly kidneys. Re-appointment with an interval of at least 8-12 hours can lead to accumulation.

Alprazolam uses

Used as an anxiolytic and antidepressant weak, for the treatment of non-psychotic disorders:

- Anxiety disorders and neuroses with anxiety, stress, anxiety, irritability, sleep disturbance, somatic disorders;

- Mixed anxiety and depression;

- Neurotic reactive depressive states associated with decreased mood, loss of interest in surroundings, anxiety, loss of sleep, loss of appetite, changes in body weight, somatic disorders;

- Anxiety, mixed anxiety-depression and neurotic depression, developed on the background of somatic diseases;

- Panic disorder (with or without phobic symptoms), panic attacks and phobias with agoraphobia.

- Neurosis and psychopathy, accompanied by a sense of unease and anxiety;

- Reactive depression (including on the background of systemic diseases); insomnia, withdrawal syndrome (in patients with alcoholism and drug addiction).

Alprazolam cautions when receiving

In the course of treatment is strictly prohibited the use of alcohol; Avoid activities that require attention, speed of mental and motor responses.

Efficacy and safety of use in patients under the age of 18 years have not been established.

Patients not taking psychotropic drugs earlier, "responsible" for the drug at lower doses compared to patients taking antidepressants, anxiolytics or suffering from alcoholism.

When endogenous depression alprazolam can be used in combination with antidepressants.

Abolition of the drug alprazolam should be carried out gradually. It is recommended to reduce the dose to 500 mg in the reception is not more than three times a day. In some cases, a slower elimination of the drug. Sudden discontinuation of alprazolam may lead to a withdrawal syndrome that manifests itself in the form of insomnia, sweating, seizures, tremors and spasms of skeletal muscles.

alprazolam pic

Enhances the effect of alcohol, neuroleptics and hypnotics, narcotic analgesics, central muscle relaxants. Increases concentration of imipramine in the serum.

Conditions and terms of Alprazolam should be protected from exposure to sunlight place, as well as children, with an air temperature of not more than 25 - 30 ° C. The shelf life of the drug Alprazolam is about a period of 4 - 5 years from date of manufacture.

Overdose Alprazolam

Symptoms overdose alprazolam: drowsiness, confusion, deterioration of motor coordination, reduced reflexes, nystagmus, speech disorder, lowering blood pressure, the development of coma.

Treatment overdose alprazolam: gastric lavage, activated charcoal, symptomatic therapy aimed at maintaining breathing and blood pressure; in a hospital - the introduction of flumazenil.

Alprazolam is contraindicated when used:

  • Severe depression;
  • Angle-closure glaucoma;
  • Choquet;
  • Acute poisoning with alcohol, drugs and psychotropic substances, as well as opioid analgesics;
  • Chronic obstructive respiratory diseases with early signs of respiratory insufficiency; myasthenia gravis;
  • Acute respiratory failure;
  • Hypersensitivity to benzodiazepines or other components of alprazolam.

Medications which contain a substance Alprazolam

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Experience with Alprazolam in the Complex Treatment of Mental Disorders

Tranquilizers (benzodiazepines) constitute one of the main classes of psychotropic drugs and have been used in clinical medicine for more than 50 years.

Currently, about 30 different preparations of the benzodiazepine structure (anxiolytics and hypnotics) are used. Despite the fact that in 1983 WHO recognized the ability of benzodiazepines to induce drug dependence, nevertheless they are still widely used not only in psychiatry, but also in other fields of medicine, and in a number of cases are irreplaceable. The development of antidepressants with a pronounced anxiolytic effect (especially selective serotonin reuptake inhibitors), anxiolytics and hypnotics of the nonbenzodiazepine structure, has led to some replacement of benzodiazepines from medical practice, but due to the specific mechanism of action providing high and rapidly developing psychotropic activity and good tolerability, they invariably occupy their niche in the treatment of neurotic psychiatric disorders

In the spectrum of action of benzodiazepines, several main effects are traditionally distinguished: anxiolytic (anxiolytic), sedative, hypnotic, myorelaxing, anticonvulsant and amnestic. Currently, for clinical practice, their anxiolytic and hypnotic actions are most important, while the rest are almost not used or are considered as side effects.

Alprazolam - a typical representative of benzodiazepine anxiolytics - to varying degrees possesses all the properties of the drugs of this group. The experience of using alprazolam in the complex therapy of mental disorders.

The main thing for him is anxiolytic action. Alprazolam refers to highly potent benzodiazepines, that is, a pronounced anxiolytic effect develops with the use of low doses of the drug. This is due to the fact that alprazolam has a higher affinity for specific benzodiazepine receptors.

There are other properties that distinguish alprazolam from other representatives of this group: the average duration of action, less severe sedation and behavioral toxicity. These features make it possible to widely use alprazolam including in outpatient practice. In addition, the therapy of mental disorders uses the ability of alprazolam to relieve manifestations of depression. It is believed that alprazolam is the only benzodiazepine tranquilizer that exhibits antidepressant activity.

The spectrum of clinical effects of alprazolam, like other benzodiazepines, is based on the modulation of GABA receptors, followed by secondary neurochemical and hormonal changes. It is discussed that stimulation of GABA-receptors leads to a change in the activity of the monoaminergic system. At the same time, the activity of the hypothalamic-pituitary-adrenal system is weakened. Long-term use of benzodiazepines, including alprazolam, leads to a decrease in the sensitivity of GABA-receptors. This is the basis for the development of the phenomenon of addiction. However, it is believed that tolerance is not formed to all the effects of benzodiazepines. It is unconditional for sleeping pills, miorelaxing and anticonvulsants and is contested with regard to anxiolytic effect. Indeed, many patients take alprazolam for a long time to relieve anxiety without reducing the effectiveness of treatment.

It is assumed that due to the selective effect on a2- and a3-subunits of GABAd receptors, the antidepressant effect of alprazolam is realized, which is absent in the spectrum of psychotropic activity of other tranquilizers, the action of which is associated with stimulation of GABA-receptors.

Interesting data on the bipolarity of the neurochemical action of alprazolam, depending on the initial emotional state: with depression, the drug contributes to the enhancement of noradrenergic activity (especially in the prefrontal cortex and hippocampus), and in case of anxiety it leads to its weakening.

Benzodiazepines do not have affinity for dopamine, serotonin, cholinergic, adrenergic, histamine and other receptors of the central nervous system and the autonomic nervous system. This determines the absence in their application of side effects, so characteristic of other classes of psychotropic drugs.

The average period for reaching the maximum concentration of alprazolam in the blood is 1.5 hours. Due to its high lipophilicity, the drug, like other benzodiazepines, penetrates well through the blood-brain barrier, which explains the rapid onset of its therapeutic effect. Alprazolam refers to benzodiazepines of average duration of action: the average half-life of the drug is 11 hours.

According to various literature sources, alprazolam has a unique, in comparison with other tranquilizers, a spectrum of psychotropic activity. The drug is most effective in the treatment of disorders, the clinical picture of which is mainly determined by anxiety symptoms of varying severity. To such conditions are primarily panic disorder, generalized anxiety disorder, various anxiety-depressive conditions, including reactive and somatogenic. In addition, alprazolam has proven itself in the treatment of obsessive-compulsive disorder, isolated phobias, abstinence states.

The effectiveness of alprazolam in the treatment of panic disorder is indicated by the results of numerous comparative studies. A number of studies indicate that in the treatment of panic disorder, compared with other benzodiazepine tranquilizers, alprazolam reduces the frequency of panic attacks to a greater extent, reduces the severity of anxiety and depressive symptoms. If we take into account the cases of partial improvement, then alprazolam is effective in 80% of cases. It is believed that in this respect, the action of alprazolam is comparable only to clonazepam. It was found that alprazolam in an average dose of 4 to 7 mg / sug. more effective than placebo for 4 weeks of follow-up. In this case, there was no direct relationship between the concentration of the drug in the blood and the effectiveness of therapy. This means that the effectiveness of treatment is more dependent not on the dose of the drug, but on clinical and psychopathological factors. In addition, it is indicated that the drug acts not only on anxiety expectations, but also on the symptoms of panic attacks themselves, reducing their severity and preventing the development of repeated panic attacks. The range of doses of alprazolam in the treatment of panic disorder is wider than in the treatment of other anxiety conditions, and is up to 10 mg / sug. (an average of 2-6 mg / day.), divided into 3-4 doses.

Numerous studies have been devoted to the use of alprazolam in generalized anxiety disorder (GAD). Symptomatic GAD is effectively reduced by alprazolam therapy at an average daily dosage of 0.5-4.0 mg, divided into 3-4 doses, in different age groups of patients, as evidenced by the results of numerous placebo-controlled studies. It was found that, in comparison with other benzodiazepine tranquilizers, the use of alprazolam is accompanied by fewer side effects. It should be noted and a relatively rapid onset of the effect, which manifests itself during the first week of treatment. Despite the high efficacy of alprazolam in GAD therapy, currently antidepressants are given preference in the treatment of this pathology. However, in this case, the role of benzodiazepines in the treatment of GAD should not be underestimated. Given the fact that the effect of antidepressants manifests itself only a few weeks after the initiation of therapy, the use of benzodiazepines at the beginning of treatment for the relief of anxiety and insomnia does not yet have an alternative. In connection with the risk of developing drug dependence, it is recommended to use alprazolam for several weeks, followed by a gradual cancellation. In cases where this period is not sufficient for the development of a stable therapeutic effect, a longer application of the drug is possible, provided that careful dynamic observation is made.

In a study of the efficacy of alprazolam in patients with gastrointestinal irritable bowel syndrome manifested by irritable bowel syndrome, a significant decrease in both anxiety symptoms (in 98% of patients) and gastrointestinal complaints (in 89% of patients) occurred after 4 weeks of therapy. The drug also proved itself in the treatment of anxiety in the context of alcohol withdrawal symptoms.

In the literature it is repeatedly mentioned that, in addition to the actual anxiolytic effect, the drug also has an antidepressant effect that has not been detected in other tranquilizers. Its presence was discovered shortly after the active introduction of alprazolam into clinical practice and was confirmed in a number of further studies. There are indications of the effectiveness of alprazolam not only with neurotic, but also with endogenous depression. In this case its effect is comparable with tricyclic antidepressants. Many authors indicate the advantage of its use in syndromes, in the structure of which there is a combination of anxiety and depressive symptoms.

There are data indicating the effectiveness of alprazolam in the therapy of premenstrual syndrome.

The successful use of alprazolam in the treatment of acute stress and obsessive-compulsive disorders is described. In this case, the drug was administered either at the beginning of the course in addition to selective serotonin reuptake inhibitors (SSRIs) for relief of severe anxiety, or as monotherapy in the resistance or intolerance of SSRIs. However, despite the proposed assumptions, alprazolam was ineffective in the treatment of posttraumatic stress disorder (PTSD).

Data on the use of alprazolam as a corrector for extrapyramidal symptoms (especially acute dystonia and akathisia) caused by the administration of neuroleptics have been obtained. However, in the presence of other highly effective remedies for neuroleptic syndrome, alprazolam can not be considered as a first-line drug.

The most common side effects with alprazolam therapy are sedation and drowsiness, which is explained by the interaction of the drug with GAM KA receptors and during the course of treatment the above-mentioned side effects are reduced to a large extent.

Termination of regular intake of alprazolam should be gradual in order to avoid the development of withdrawal syndrome. During this period, from a few weeks to months, the daily dosage of the drug is gradually reduced to a complete cancellation. A number of studies have noted that a decrease in the dose of benzodiazepine tranquilizers may be accompanied by a withdrawal syndrome and the return of clinical manifestations of the underlying disease, especially in cases of abrupt discontinuation of therapy.

Despite the prevailing view that there is a risk of drug dependence, numerous studies have shown that the frequency of dependence among patients receiving alprazolam is relatively small. The authors note that the dependence on benzodiazepines is a relatively rare phenomenon and is found mainly in people who abuse alcohol or drugs.

Some other side effects of alprazolam should be mentioned. A number of studies have revealed a deterioration in the processes of perception and reproduction of new information. This feature must be taken into account when driving. It is important to note the interaction of alprazolam with alcohol, tk. Many patients with anxiety symptoms themselves resort to taking alcohol to ease the condition. Their combined use leads to a significant deterioration in the results when performing psychological tests, and in a number of patients increases aggression and irritability.

Thus, as shown by numerous data, including recent years, alprazolam remains a very popular and effective tranquilizer. However, many questions require clarification and further study. In particular, the place of alprazolam in the complex therapy of psychiatric disorders needs to be considered along with new drugs from other psychopharmacological groups. The questions concerning the applied dosages of alprazolam, the possible duration of its use, as well as the frequency and conditions for the formation of dependence remain unclear.

Patients with depressive disorders, including endogenous and neurotic depressions, in our study accounted for more than half of all observations - 58.2%. In most cases, the symptoms of anxiety were noted in the structure of the depressive syndrome, which was an indication for the appointment of aprazolam, especially in the first weeks of therapy, before the anxiolytic effect of antidepressants. In the primary depressive episode and recurrent depression, alprazolam was mainly used in combination therapy with antidepressants of various generations (maprotiline, azaphene, paroxetine, mirtazapine, simbalt, valdoxan, etc.), small doses of some neuroleptics (sulpiride). In a number of cases, sleep disturbances were additionally assigned hypnotics (zopiclone). Treatment for depression in bipolar disorder (BAP) had its own characteristics, taking into account the possibility of transition to the manic phase, especially with BAP-1. Antidepressants were used, not causing an inversion of affect. Already during the arresting therapy, anticonvulsants (vapiropats, carbamazepine), antipsychotics (quetiapine, olanzapine) were prescribed, which patients continued to take during remission as maintenance therapy. With BAP-11, depressive symptoms were stopped by antidepressants from the SSRIs group, venlafaxine, valdoxan in combination with alprazolam, which has an anxiolytic effect, especially in the first weeks of therapy before the development of the antidepressant's own effects, and antidepressant potentiating them. Of anticonvulsants, lamotrigine and valproic acid preparations were preferred, and quetiapine was used for antipsychotics. In almost half of cases of neurotic depression (12 people), alprazolam was used as monotherapy, at a dose of 0.75-1 mg for 4-7 weeks with good effect, i.e. almost complete recovery.

This once again indicates the presence of alprazolam antidepressant effect.

Many patients with depression had symptoms of somatic anxiety (including somatized depression), which disappeared along with mental anxiety. Perhaps, in this case, we can talk about the vegetotrophic action of alprazolam, as well as other benzodiazepines (phenazepam, diazepam). Perhaps another explanation: along with anxiety, her somato-vegetative "escort" also departs.

In anamnesis of many patients with panic disorder, anxiety-phobic disorders, recurrent depression, episodes of effective use of alprazolam with tianeptine with a fairly rapid reduction of symptoms and the restoration of social functioning were noted.

With organic brain lesions, alprazolam was used as an anti-anxiety and sedative in combination with small doses of sedative antipsychotics (clozapine, olanzapine), nootropics. Duration of therapy - no more than a month, daily doses - up to 0.75 mg. Antipsychotics in these cases were prescribed as behavior correctors, and alprazolam "softened" the side effects.

With sluggish schizophrenia, alprazolam was administered within the polymorphic neurosis-like syndrome, which included anxious, panic, obsessive-compulsive and depressive disorders. As a rule, it was used in combination with antidepressants (rexetin, mirtazapine, amitriptyline), neuroleptics (sulpiride, sonapax, chloroprotoxen, quetiapine), hypnotics (zopiclone, zolpidem), short courses from two to four weeks at a dose of 0.5-0, 75 mg per day.

A special group consisted of patients with paranoid schizophrenia, to which alprazolam was prescribed in addition to neuroleptics (clozapine, olanzapine, paliperidone, risperidone) as an anti-anxiety agent and a potentiating sedative effect. This made it possible to reduce the dose of antipsychotics, which is especially important when performing treatment in an outpatient setting in order to improve social adaptation and quality of life. The courses of therapy of different duration, from two weeks to several months, depending on the indications, the dose of the drug - 1-1.5 mg per day.

Thus, the study confirmed that alprazolam has a high anxiolytic activity, even in small doses with a slight expression of sedative and hypnotic effects, which allows its use as a day tranquilizer and anxiolytics in patients with a wide range of anxiety-phobic and panic disorders of various origins. Alprazolam advantageously differs from other benzodiazepines by the presence of antidepressant action, therefore it can be used to treat not only anxious, but also depressive disorders. There is a good tolerance and high safety of the drug, as well as a practical lack of risk of drug dependence when using small doses and strict observance of indications for use. Alprazolam can be prescribed in inpatient and outpatient settings, both in short courses and for a long time, depending on the nature of the mental disorders.


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Interaction of the Alprazolam with Alcohol

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