BENZODIAZEPINES: MECHANISM OF ACTION, USES AND EFFECTS - NEUROPSYCHOLOGY - 2024

The benzodiazepines are psychotropic drugs which act directly on the central nervous system. By acting on the brain regions they produce sedative, hypnotic, anxiolytic and anticonvulsant effects.

Benzodicepines are used in medicine as a treatment for anxiety disorders, insomnia and some affective states. Likewise, they can be incorporated into the intervention of pathologies such as epilepsy, alcohol withdrawal and muscle spasms.

At present, these drugs are considered the most effective for treating anxiety disorders, due to the good results they present and the few side effects they cause.

In the commercial field, you can find multiple benzodiapin drugs, most of them are usually characterized by the ending lam or pam. The best known are alprazolam, diazempam, flurazepam, and lorazepam.

Mechanisms of action of benzodiazepines

Mechanisms of action refer to the method by which benzodiazepines act when they reach the brain and manage to make changes in psychological functioning.

Benzodiazepines act directly on an inhibitory neurotransmitter in the brain known as gamma animo butyric acid (GABA), binding to specific receptors for this neurotransmitter and acting as a GABA agonist.

This means that when benzodiazepines reach the brain regions, they increase the activity of GABA and, therefore, the postsynaptic inhibitory potentials are increased.

The main advantage of benzodiazepines is that when they act on GABA, they increase the opening frequency of the chlorine channel. Thus, these drugs are not capable of providing greater activation than GABA alone would achieve, so the risks of their consumption are low.

GABA receptors

GABA receptors act as drug targets for various clinically useful compounds. It consists of a receptor of ion channels that are formed through protein combinations.

Likewise, most GABA receptors are made up of 5 subunits: a 1 subunit, 2 subunit, 3 subunit, 4 subunit and 5 subunit.

In this sense, different benzodiazepine drugs have been composed that act on the different subunits of the GABA receptors.

Recent research has shown that, more specifically, benzodiazepines that act on the a1 subunits have anxiolytic activity, while those that act on the a3 or a5 subunits have sedative effects.

In summary, benzodiazepines carry out their effects by increasing the activity of GABA, a neurotransmitter in the brain that is responsible for inhibiting brain function.

Many disturbances of anxiety or agitation respond to a decrease in the functioning of these substances. In these cases, the use of benzodiazepines is very useful since it allows to restore brain function.

Pharmacokinetic characteristics

Central chemical structure of the benzodiazepine ring system.

The pharmacokinetic characteristics refer to the method by which benzodiazepines reach the brain regions when consumed.

This process depends mainly on the characteristics of the drug rings (their structure), which determine the degree of lipid solubility and metabolism of the drug.

Three main procedures can be distinguished in the pharmacokinetics of benzodiazepines: absorption, distribution, and metabolism.

Absorption

Benzodiazepines are taken orally. They are substances that are usually absorbed very well and with some ease.

The rate of absorption depends on the fat solubility of the drug. In the case of benzodiazepines, it usually takes between 30 and 240 minutes.

Thus, the absorption of these drugs, despite being adequate, can be somewhat slow and irregular. For this reason, in emergency cases such as seizures or panic attacks, intravenous administration is usually recommended, which allows much faster absorption.

Metabolism

Benzodiazepines are metabolized at the microsomal hepatic level, through oxidation, dealkylation and hyroxylation processes. This mechanism allows the substance to enter the person's bloodstream and circulate through the blood to the brain regions.

The particles of the substances that do not pass into the blood are conjugated with glucuronic acid or sulfate and finally eliminated by the kidney.

What are they for? Applications

Currently, benzodiazepines have multiple therapeutic uses. These drugs include a large number of molecules that share certain properties and that allow different brain disorders to intervene.

It should be noted that not all benzodiazepine drugs have exactly the same characteristics. And therefore, they do not have the same advantages for all therapeutic uses.

For example, clonazepam has a very effective profile as an anxiolytic in treating panic or general anxiety disorders and seizures.

In his case, the fact that its hypnotic, muscle relaxant and amnesic properties are low, make it a good therapeutic option for these disorders but less indicated for the intervention of other pathologies.

In this sense, the main therapeutic indications for benzodiazepines and the most indicated drugs for each condition are:

Anticonvulsants

Benzodiazepines are powerful anticonvulsants that can potentially save a person's life while managing status epilepticus.

In these cases, the most effective drugs are diazepam and lorazepam, this being relatively more effective according to a meta-analysis of 11 recently published clinical trials. However, diazepam has a much longer duration of action than lorazepam.

Although these drugs are useful to intervene in diseases such as epilepsy, side effects such as tolerance or drowsiness make them not the drugs of first choice to treat these conditions in the long term.

Today it is concluded that benzodiazepines are very useful drugs to treat specific seizure symptoms. But not to be used as long-term therapeutic tools.

Anxiolytics

Anxiety problems are probably the conditions in which benzodiazepines have been shown to be most effective. These medications have important anxiolytic properties and can be used for the temporary management of severe anxiety.

Benzodiazepines to treat anxiety are usually consumed orally, although they can be administered intravenously in cases of panic attack, since in this way the time of action of the drug is reduced.

The high anxiolytic potential of benzodiazepines has motivated them to be considered today as the main drugs for the treatment of anxiety disorders.

Specifically, alprazolam, bromazepam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, medazepam, nordazepam, oxazepam and prazepam are the most effective and used.

However, these drugs have the same limitations as benzodiazepines for anticonvulsant purposes

The risk that benzodiazepines have of generating tolerance and dependence in the consumer is high, which is why it is recommended to limit their use to short periods of time (between 2 and 4 weeks).

Insomnia

Benzodiazepines may also be suitable therapeutic tools for the treatment of insomnia.

Its use is recommended for limited periods of time due to the risks of generating addiction and dependence. In this sense, the intermittent use of benzodiazepines is especially useful in the treatment of insomnia.

These drugs make it possible to improve sleep-related problems by shortening the time it takes to fall asleep, prolonging the time you sleep, and reducing wakefulness.

However, its consumption usually worsens the quality of sleep, increasing light sleep and decreasing deep sleep.

Thus, despite their efficacy, the use of benzodiazepines for the treatment of sleep-related problems should be done with moderation and vigilance.

In general, its use is recommended in serious alterations and by means of an exhaustive medical control to avoid the negative effects that the consumption of the psychotropic drug can produce.

Use prior to surgery

Benzodiazepines are one of the most widely used medications to alleviate symptoms or anxious sensations in subjects who are in the previous moments of a surgical procedure.

They are usually administered two or three hours before surgery, a fact that allows to alleviate anxiety symptoms and produce amnestic effects, which help to forget the discomfort prior to the operation.

Benzodiazepines are also used in cases of dental phobia and in ophthalmological procedures.

Intensive care

Benzodiazepines are drugs highly used in the treatment of patients found in intensive care units.

Especially in subjects receiving artificial respiration, patients with very high pain or individuals with high feelings of anxiety and discomfort, the administration of benzodiazepines allows to alleviate and relax their state.

However, caution should be exercised in their use since in some cases benzodiazepines can cause respiratory depression.

Alcohol dependence

Benzodiazepines have been shown to be safe and effective drugs in the treatment of alcoholic assist symptoms.

Specifically, the most widely used are diazepam and chlordiazepoxide, long-acting drugs, and lorazepam and oxazepam, intermediate-acting drugs.

Diazepam and chloridazepoxide make withdrawal symptoms less severe and thus facilitate the detoxification process.

For its part, oxazepam is the most widely used benzodiazepine in the treatment of severe withdrawal syndromes and in patients who metabolize drugs with greater difficulty, such as the elderly or patients with liver cirrhosis.

Muscle disorders

The consumption of benzodiazepines causes high muscle relaxation and are useful drugs for the control of spasms. The most commonly used drugs for these purposes are baclofen and tizanidine.

However, it must be borne in mind that prolonged use of these drugs can cause the patient to develop tolerance to their relaxing effects.

Mania

Manic episodes of bipolar disorders are often treated with mood stabilizers. However, in some cases, the administration of benzodiazepines may be adequate for the short-term management of some symptoms.

Benzodiazepines such as clonazepam or lorazepam make it possible to quickly calm and sedate the subject, and mitigate some manifestations of mania such as agitation or nervousness.

Contraindications

Although the therapeutic effects of benzodiazepines are adequate to treat multiple disorders, these drugs also have a number of contraindications. In general, the use of these drugs is not recommended in:

1. Patients with angle-closure glaucoma, since the possible anticholinergic effect of benzodiazepines can aggravate the disease.
2. In cases of muscular hypotonia or myasthenia due to the relaxing effect of the smooth muscles caused by benzodiazepines.
3. In subjects with severe respiratory failure and sleep apnea.
4. In patients with liver failure as the risk of encephalopathy is increased.
5. In cases of acute alcohol intoxication, coma or syncope, due to the depressive effect produced on the central nervous system.

Effects and adverse reactions

The consumption of benzodiazepine drugs can cause adverse effects in the subjects who consume it.

The toxicological profile of the different benzodiazepine drugs is very similar, although in some cases the frequency and severity of symptoms may vary.

In most cases, adverse reactions occur due to a prolongation of the pharmacological action of the drugs, a fact that affects the functioning of the central nervous system.

Different studies indicate that approximately half of the patients present, to a greater or lesser degree, feelings of drowsiness during the first moments of treatment.

Likewise, other adverse effects that may appear are:

1. Sedation.
2. Dizziness, nausea, and vomiting
3. Diarrhea or constipation
4. Depression and mood swings.
5. Changes in libido
6. Disorientation.
7. Dysarthria and tremor.
8. Urinary disorders.
9. Hepatites, jaundice, dermatitis, urticaria and cigarillo.
10. Blood dyscrasias.
11. Vision and hearing disorders.
12. Motor incoordination with risk of falling.
13. Anterograde amnesia and difficulty concentrating.

References

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