6. Anxiolytics (tranquilizers)

The main for these substances is anxiolytic (tranquilizing) effect. It manifests itself in reducing internal stress, eliminating anxiety, anxiety, and fear. Most anxiolytics have a sedative effect. Anxiolytics are used mainly in neurotic and neurosis-like (reactive) states.

Anxiolytics are represented by the following groups of drugs:

1. Benzodiazepine receptor agonists (diazepam, phenazepam, etc.).

2. Serotonin receptor agonists (buspirone).

3. Substances of a different type of action (amisyl, etc.).

The first group of substances is most widely used.

Classify benzodiazepine anxiolytics by duration of action.

1. Long-acting (t _1/2 = 24-48 h)

Phenazepam Diazepam (sibazon, seduksen, valium)

Chlordiazepoxide (hlozepid, Elenium)

2. The average duration of action ( t _1/2 = 6-24 h)

Nozepam (oxazepam, tazepam)

Lorazepam alprazolam

3. Short acting (t _{l / 2} <6 h)

Midazolam (dormicum)

The following effects are characteristic of benzodiazepine drugs: anxiolytic, sedative, hypnotic, muscle-relaxing, anticonvulsant, amnestic.

Reduced benzodiazepines have pronounced anxiolytic and sedative properties. Reducing emotional stress contributes to the onset of sleep. Psychotropic effects are associated with their influence on the limbic system. Thus, it has been shown that benzodiazepines to a greater degree reduce the spontaneous activity of the neurons of the hippocampus than the hypothalamus and the reticular formation of the brain stem. They suppress the impulse aftereffect in the limbic system, as well as in the hypothalamus. Something important is the inhibitory effect on the activating reticular formation of the brain stem.

The mechanism of action of benzodiazepines is associated with GABAA receptors. During stimulation of benzodiazepine receptors, allosteric activation of GABAA receptors is observed. Therefore, the interaction of benzodiazepines with the receptors of the same name manifests itself in the form of a GABA-mimetic effect (the incoming current Cl increases). There is hyperpolarization of the membrane and inhibition of neuronal activity.

The most effective anxiolytic is phenazepam. In anxiolytic and hypnotic effects, it is superior to diazepam.

Benzodiazepines are distinguished with a pronounced anxiolytic effect and no or minimal sedative-hypnotic effect. Such drugs are sometimes referred to as “daily anxiolytics (tranquilizers). These will be attributed to the Mezapam (Rudotel).

Benzodiazepines cause myorelaxation by inhibiting spinal polysynaptic reflexes. Benzodiazepines have anticonvulsant activity. In large doses, they can cause amnesia. Potentiate the inhibitory effect on the central nervous system of substances with a narcotic type of action.

Benzodiazepines easily penetrate the blood-brain and other biological barriers. Well absorbed from the digestive tract, mainly from the duodenum.

Diazepam is absorbed the fastest, and nozepam, lorazepam more slowly; intermediate position occupied by alprazolam, midazolam.

Some metabolites have a pronounced and prolonged anxiolytic effect. For example, the metabolite of chlordiazepoxide and diazepam N-desmethyldiazepam (nordiazepam), the reduction of which in plasma by 50% (t _1/2 ) occurs in the range of 40-200 hours.

With their use, side effects can occur: drowsiness, slowed motor reactions, memory impairment, weakness, diplopia, headache, nausea, irregular menstrual cycle, decreased sexual potency, skin rashes. With long-term use of benzodiazepines (about 6 months), addiction develops, drug dependence (mental and physical) may occur.

A specific benzodiazepine antagonist is flumazenil. Flumazenil is usually used to eliminate the residual effects of benzodiazepines (for example, when used in surgical practice or diagnostic procedures), as well as in their overdose or acute poisoning.

The agonists (partial) of serotonin receptors include buspirone. It has a high affinity for serotonin receptors of the brain subtype 5-HT _1A .

It leads to a decrease in the activity of neurons in the suture nucleus, a decrease in the synthesis and release of serotonin. In addition, buspirone binds to dopamine receptors. Does not interact with benzodiazepine receptors, there is no GABA effect. It has a rather pronounced anxiolytic activity (close to that of sibazon). The effect develops slowly (within 1-2 weeks). The drug has no sedative, anticonvulsant and muscular-relaxing effects, the ability to cause addiction and drug dependence is poorly expressed.

Side effects are sometimes marked by nervousness, dizziness, headache, paresthesias, nausea, diarrhea.

To the group of anxiolytics of a different type of action, the derivative of diphenylmethane is amisyl (benactisin). He belongs to the group of central anticholinergics. Its sedative effect is obviously to a certain extent due to the inhibition of the m-cholinergic receptors of the reticular formation of the brain. Amizil eliminated the reaction of EEG activation caused by cholinomimetics, had a synchronizing effect. Amizil enhances the effect of narcotic-type substances and opioid analgesics. It has anticonvulsant activity. Suppresses the cough reflex.

For amisyl, a peripheral m-anticholinergic action is characteristic, as a result, smooth muscle spasms are reduced, pupils dilate, gland secretion is inhibited. Amisyl has anesthetic and anti-histamine properties.

Anxiolytics also include trioxazine, oxylidine (benzoclidine hydrochloride) and a number of other drugs.

Anxiolytic properties are also found in β-blockers.

Preparations of this group are used mainly for neurosis and neurosis-like conditions. They are prescribed for sedation before surgery. They are widely used for insomnia. Benzodiazepines are effective in status epilepticus (administered intravenously with neurological disorders involving skeletal muscle hypertonus. Patients whose professions require special attention and are fast; reactions (eg, transport drivers) should not be given benzodiazepines on an outpatient basis.

SEDATED MEANS

Sedatives include bromine salts (bromides), valerian preparations, and motherwort preparations. They all have a mild sedative effect.

Of the bromine salts, sodium bromide and potassium bromide are most commonly used. Their main action is associated with increased inhibition in the cerebral cortex. The effect of bromides depends on the type of the nervous system and its functional state (with a weak type of nervous system, smaller doses are necessary than with a strong type). The effect of bromides in neurosis is most pronounced. Bromides have antiepileptic properties, but are significantly inferior in activity to other drugs used for epilepsy.

A 50% reduction in plasma bromine occurs after about 12 days. Traces of bromine are detected after 1 month or more.

Apply bromides for neurosis, irritability, insomnia. Due to the slow elimination of bromides from the body, they cumulate and can be the cause of chronic poisoning - bromism. This is manifested by general lethargy, apathy, memory impairment; skin lesions are typical (aspe bromica). Irritant effect of bromides leads to inflammation of the mucous membranes, which is accompanied by cough, runny nose, conjunctivitis, diarrhea.

Valerian preparations (infusion, tincture, extract , which contain essential oil (ether of borneol and isovaleric acid), valeric acid, borneol, organic acids, some alkaloids, tannins) are widely used as sedatives.

Sedative properties also have herbs of motherwort (tincture, tincture), made from motherwort five-bladed (Leopurus quiipquelobatus) and motherwort (Cardiac leopurus). They contain essential oil, alkaloids, saponins, tannins. According to the indications for the use of herbs motherwort similar to drugs Valerian.