Benzodiazepines: mechanism of action, use and safety

The last decade is characterized by a realistic assessment of the risk / benefit ratio of the benzodiazepines. First of all, this is due to the development of clear approaches to minimizing the negative effects of benzodiazepine tranquilizers. Gradually benzodiazepines returned to the pedestal of the most popular psychotropic drugs. Suffice it to say that the key representative of the diazepam is included in the list of necessary medicines compiled by the World Health Organization, which determines the minimum set of medicines needed in the health care system. Approximately 10% of people in the population resort to using the database at least once a year. At the same time, only 16% of appointments are carried out by psychiatrists, a large proportion (55%) of prescribing the database belongs to general practitioners. These data allow us to state the stable use of the database for multifactorial indications, which, of course, reflects the emerging balanced position of different medical specialists with respect to this class of drugs.
The benefits of therapy with benzodiazepine drugs and potential risks are related to the fact that directly or indirectly the database affects virtually all aspects of the nervous system functioning.

Mechanism of action

Benzodiazepine drugs enhance the action of the natural brain mediator – g-aminobutyric acid (GABA). The work of about 40% of the brain nerve cells is provided by GABAergic mediation, due to which the general inhibitory effect on the brain is realized. There are several benzodiazepine receptors subtypes (GABA) (6 different a-subunits, 4 different b-subunits, 3 different g-subunits), differing in their effects. For example, the a1 receptors subtype is predominantly responsible for sedation, a2-subtype is responsible for the anti-anxiety effect. At the same time, the joint activation of the a1 and a2 benzodiazepine receptors subtypes, as well as the a5 subtype, provides an anticonvulsant response. All benzodiazepine preparations combine to a greater or lesser extent with all receptor subtypes, however, different affinities for individual receptors may provide some differences in the various members action spectrum of this class. The each derivatives affinity of the benzodiazepines to these receptors reliably correlates with the severity of the psychotropic effect of the drug.
The different subtypes discovery of the GABA-receptor and regulation of tonic GABA inhibition supports the latest research in the selective databases development. Thus, new subclass Z representatives (zaleplon, zoldipem and zopiclone) selectively bind to the a1 GABA-A receptor subunits and are positioned only as hypnotic agents. Recent developments indicate the two inhibitory effect provision types of GABA on the brain. The trigger of phasic inhibition is the peak concentration of GABA released into the synapse. Phasic inhibition – the basis of the habituation effect to the database. Phasic activity is provided through OBD-sensitive GABA receptors containing g, a (1-3) and a5 subunits located intrasynaptic. In contrast, GABAA receptors containing a4, a6 and g1 subunits, localized extrasynaptic, regulate tonic inhibition. The medications creation that selectively affect tonic inhibition will help to level the addiction problem to anxiolytic therapy.

Use in acute conditions

Acute stress. Acute stress reaction is called symptoms, including anxiety, which arise sharply in response to exceptional stressful events. Symptoms unfold quickly and sometimes last long enough. Diazepam is widely used in medicine for disasters to correct reactions caused by extreme stressors (catastrophic disasters). When cupping diazepam of acute stress-related reactions, it is preferable to use short courses. However, prolonged use of diazepam may interfere with normal psychological adaptation after a psychological trauma. For example, diazepam perfectly inhibits the grief reaction with the loss stress, the agitation symptoms . But if you use the drug uncontrollably long after stress, then the reaction may not be resolved to the end and persist for many years. In addition, a decrease in the level of attention in the use of the database can limit the patient’s learning ability to alternative strategies for coping with stress, including cognitive behavioral therapy. Therefore, it is desirable to stop diazepam acute condition (short course 1-3 weeks), and then or in parallel to connect cognitive psychotherapeutic techniques.
It is important that diazepam reduces the plasma cortisol level, a activation marker of the hypothalamic-pituitary-adrenal system during the stress period. Excess cortisol levels not only prolong the affective post-stress disorders, but also slow the hippocampal structures neurogenesis, which in the long run may increase the risk of developing cognitive impairment. Recently, in experimental studies on animal models of acute stress, the protective effect of a single dose of diazepam on the striatum cells damage by products of oxidative stress in an acute period has been shown. This preventive action allows, along with anxiolytic, to discuss the antioxidant diazepam effect and treat it as a universal remedy in the acute stress phase.
Epileptic status. Epileptic status is a medical condition requiring emergency care associated with a high risk of death. Epileptic status is characterized by epileptic seizures lasting more than 30 minutes or a cluster of seizures without complete consciousness recovery. Benzos – preparations of the 1st line for the relief of epileptic status and drug-induced seizures. The diazepam effectiveness in the cupping of the status is 80%. From the point of view of the most effective maintenance of the status, it is recommended to start diazepam in case the attack lasts more than 5 minutes. Initially, 20 mg of diazepam is administered; if seizures continue, intravenous drip diazepam is injected at 100 mg per 500 ml of a 5% glucose solution at a rate of 40 ml/min, which guarantees a therapeutic concentration of the drug in the blood.
Premedication (application in anesthesiology). Benzos is widely used for preoperative sedation, increased intraoperative amnesia, and sometimes as an introductory drug for general anesthesia and potentiating its effect. The benzos application also shown when general anesthesia is impossible or too risky. In particular, diazepam is often prescribed to patients with an unstable condition before an emergency cardioversion. Some authors recommend using DB in resuscitation practice to “postpone” the increase in oxygen demand in seriously ill patients, especially when patients with combined respiratory and cardiovascular insufficiency need to carry out certain manipulations.

Chronic use

Anxiety disturbance disorders. Indications for the use of benzodiazepine tranquilizers cover the whole spectrum of anxiety-phobic conditions. Benzodiazepines reduce not only the actual anxiety manifestations (fear, internal tension sensation, irritability, agitation), but also somatic (vegetative) anxiety symptoms, such as palpitation, air lack sensation, sweating, tremor. The anxiolytic effect is associated with the limbic complex suppression and other brain anxiolytic zones, as well as the indirect influence on most neurotransmitter systems. The main advantage of the benzos, especially diazepam, is the rapid development of the effect, usually after the first dose. This immediate effect contrasts with the antioxidant effect of antidepressants. In addition, the database is non-toxic and easily transferred. Immediate effectiveness and safety allow us to treat the benzos as first choice drugs for rapid reduction of anxiety and distress. Intermittent courses lasting 2-4 weeks are most often used during periods of increased anxiety level when generalized anxiety disorder fluctuates. In panic disorder, the database is used to stop panic attacks (most often diazepam) or courses (up to 4 weeks) in monotherapy or in conjunction with antidepressants.

Safety

The safety of using benzodiazepine anxiolytics is due to a large range between therapeutic and lethal doses, the adverse effects absence on vital body systems. Data showing the lethal complications possibility in the treatment of benzodiazepine drugs in therapeutic doses, to date, no. Extremely rare and fatal outcomes with an accidental or intentional overdose, in connection with which for this class of drugs is problematic even the very definition of the minimum lethal dose. Benzodiazepines don’t have clinically significant effects on liver function, endocrine and urinary system. If you’re looking for the best place to buy benzodiazepines online, visit RC’s online store to place an order.

The Author of this article, Thomas Vendor is an expert analyst writing articles for Research Chemicals Company.

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