Antipsychotic drugs (neuroleptic agents).

Anxiolytics (tranquilizers).

• Drugs in this group are used for violations of human mental activity. They are used in the treatment of psychosis, as well as the neurotic and neurotic disorders accompanied with standing stress, fear, worry, anxiety and other symptoms. The mechanisms of action of psychotropic substances investigated only to a small extent, although the extent of such research are great. The most interesting information on the effect of these substances on the interneuron transmission to the exchange of biogenic amines in the cholinergic system of head of the brain to interact with peptides with amino acids that provide stimulating and inhibitory effect on neurons, etc.

• For some neuroleptics (e.g., phenothiazine derivatives) in the development of psychotropic effects can be set to their blocking effect on the serotonin receptors and m-cholinergic receptors in the brain. Antipsychotics in chemical structure related to the following group memory. 1.Derivatives of phenothiazine

• Chlorpromazine Triftazin • Etaperazin Ftorfenazin • 2.Derivatives of thioxanthene

Chlorprothixene• 3. Derivatives of butirofenone• Haloperidol

4. Derivative dibenzodiazepina • Clozapine

• The most typical representative of phenothiazine is chlorpromazine (chlorpromazine hydrochloride, largaktil, plegoma-zine, hlorazin, fenaktil, propafenin). Chlorpromazine has a wide range of actions. The drug has expressed ¬ zhennoe effect on the central nervous system, as well as peripheral nerve, executive bodies and metabolism. Effect on central nervous system is manifested in a number of effects. So, for chlorpromazine as one of the main representatives of antipsychotic neuroleptic characteristic and sedation, as well as the ability to cause extrapyramidal disorder (long-term use).

• In large doses, chlorpromazine is a hypnotic effect: light sleep comes easily interrupted by external stimulation. Typical of chlorpromazine is a decrease in motor activity (muscle relaxant effect). This is due to inhibition of supraspinal regulation of muscle tone. In particular, chlorpromazine reduces or completely eliminates the floor descending facilitating effect of the reticular formation on spinal reflexes. Directly on the spinal cord chlorpromazine does not work. In addition, chlorpromazine inhibits the center of thermoregulation. Final effect depends on the ambient temperature. Most often, there is a slight hypothermia (due to the increase of heat transfer).

• At the same time, when combined with chlorpromazine natural cooling occurs marked reduction in body temperature. Chlorpromazine has a distinct anti-emetic effect, which work by blocking the chemoreceptor trigger zone (trigger zone), located at the bottom of the IV ventricle. With this chlorpromazine preanticipates vomiting caused by apomorphine, morphine, protivoblastomnymi means of mustard group. One of the manifestations of the effect of chlorpromazine on the central nervous system is its ability to potentiate the effect of a number neyrotrop the fixed assets - facilities for anesthesia, sleeping pills, narcotic analgesics. However, the strengthening of their effects, in part due to the inhibition of aminazine processes of biotransformation of these drugs.

• Chlorpromazine has an effect on the peripheral nerve. The most ¬ more pronounced in his α-adrenoceptor blocking action. So, for example, against the backdrop of chlorpromazine pressor response to adrenaline is sharply reduced or comes "perversion" effect of adrenaline and blood pressure pa ¬ give. In addition, some peculiar aminazinu m-anticholinergic (atropine) properties. This is evident not great ¬ decreased secretion of salivary, bronchial and digestive glands. Transfer of excitation in the autonomic ganglia, he does not break. Chlorpromazine affects not only the efferent, but also on the afferent innervation. When the local action it causes marked irritation, which is replaced by anesthesia. In chlorpromazine there is significant antihistaminic activity (blocking H1-receptors). He is a ¬ is also myotropic antispasmodic action.

• It is characteristic of chlorpromazine its effect on the cardiovascular system. The symptom is more or less pronounced decrease in arterial pressuretion. The mechanism of hypotension is quite complex. It is linked to the oppression centers of the hypothalamus, with α-adrenergic blocking and antispasmodic properties of chlorpromazine, with the suppression of compensatory vasoconstrictor reflexes, as well as with a reduction in force of heart contractions.

• Hypotension is usually accompanied by a reflex tachycardia. Furthermore, chlorpromazine marked antiarrhythmic properties.

• With prolonged use of chlorpromazine to it develops addictive. However, this applies only to the sedative, hypotensive, and a number of other effects, antipsychotic action is not changed. The group of phenothiazine derivatives is also a large number of other drugs. In general, they are similar to aminazinu and differ from it only by the severity of the individual properties. Of great interest are compounds in which a side chain kidney related phenothiazine nitrogen atom, a piperazine ring. This group includes meterazin, etaperazin, triftazin, ftorfenazin etc.

• Meterazin (prochlorperazine maleate, Compazine) has potent antipsychotical activity. According to the sedative effect of losing aminazine). It has a 3-5 times greater antiemetic activity. Muscle relaxation is less than chlorpromazine. Hypotensive effect, adrenoblocking, anticholinergic and spazmolitical properties, antihistaminic activity are less pronounced (approximately 2-fold) than chlorpromazine. This characterizes meterazin with a favorable side, as rehese effects are undesirable.

• Has similar properties etaperazin (perphenazine, Trilafon). It is an assetion antipsychotic and sedative. It also relates to the most effective anti-emetic agents (chlorpromazine greater than 5-10 times). Atropine, crampinglytic and antihistaminic properties are expressed in his less than chlorpromazine.

• Much in common with the last two neuroleptics in Triftazin (trifluoperazina hydrochloride, stelazin, fluperin). Compared with the aminazine it is characterized by a more selective antipsychotic effection and less sedating effect. According to the antiemetic effect exceeds chlorpromazine. It differs from the weaker hypotensive, adrenoblocking and relaxing effect. Ftorfenazin (fluphenazine hydrochloride, DITT, Mirren) in efficiency as an antipsychotic similar triftazin. As an antiemetic slightly exceeds triftazin. This released a neuroleptic drug in the form of prolonged action - ftorfenazina decanoate (DITT depot, on flufenazindecanoate), whose action continues 7-14 days and more.

• Phenothiazine drugs row cause a variety of side effects. This may be a general lethargy, apathy, drowsiness, dry mouth, discomfort in the heart, in the epigastric region; impact hypotension, orthostatic collapse (all this is more often observed when using chlorpromazine). Sometimes develop congestive jaundice (usually in the appointment of chlorpromazine). For a number of phenothiazine neuroleptics (especially for products containing piperazine ring) are characteristic of extrapyramidal disorders (Parkinson's disease). With prolonged use of neuroleptics may develop depression. Often there are diarrheal disorders - loss of appetite, nausea. Phenothiazines cause irritation of skin and mucous shells check.

• Irritability may occur on routes of administration preparations (into a vein, muscle, enteral). Severe complications include leukopenia, and agranulocytosis. At the medical staff and the persons associated with the manufacture and packaging of phenothiazine derivatives are relatively common ¬ Xia allergic skin lesions. The derivatives thioxanthene is chlorprothixene (truksal). It is chemically similar to chlorpromazine. Characterized in that, as compared with phenothiazine in tioksantenic heterocycle in place of nitrogen is a carbon atom having a double bond. According to anti-psychotic action chlorprothixene inferior fenotiazinic pro water. The drug is interesting because it also has some antidepressive activity.

• Of great interest as antipsychotic drugs are derivatives of butirofenone. From this series of compounds for the treatment of mental illness is mainly used haloperidol (halophytes). Its action occurs relatively quickly and lasts a long time. When administered into the maximum concentration in the blood plasma observed after 2-6 hours and kept at a high level for about 3 days. After 5 days kidneys displayed about 40% of the injected substance. High antipsychotic activity of haloperidol combined with a mild sedative effect. The mechanism of action of psychotropic haloperidole associated with the blockade of dopamine receptors in the central α-adrenergic blocking properties, as well as in violation of the inversetion process of neuronal uptake of norepinephrine and deposition.

• Haloperidol in small doses blocks the chemoreceptors trigger zone of the vomiting center. Potentiates the action for narcosis, governmental hypnotic and narcotic analgesics. In contrast to haloperidol, phenothiazines not shorten REM sleep. At therapeutic doses of haloperidol and atropine no ganglioblocking properties, it significantly inhibits the peripheral α-adrenergic receptors. Blood pressure usually does not reduce orthostatic collapse does not cause. Of the side effects of haloperidol is most likely to breachtion of the extrapyramidal system (Parkinson's). Skin reactions may be. Rarely leykopoeza oppression. In case of overdose appear anxiety, fear, sleeplessness.

• Butirofenona derivative is also the drug droperidol. It differs from a short-acting haloperidol. Droperidol is used mainly in neuroleptanalgesia (in conjunction with a painkiller - fentanyl). The derivatives dibenzodiazepina is clozapine (leponeks, azaleptin). It has high antipsychotic activity. At the beginning of the application can cause marked sedation, which soon passes. Much less frequently and to a lesser extent than other neuroleptics cause extrapyramidal effects, which is a significant advantage of the drug.

• Features of the pharmacodynamics of the drug, possibly due to the fact that, according to existing ideas, classical neuroleptics and clozapine (phenothiazine derivatives, butyrophenones) interact with different types of dopamine receptors. It should also be noted that clozapine very pronounced blocking activity against M-cholinergic receptors in the brain. Clozapine is well tolerated. However, the treatment they need to be under the control of peripheral blood, as one group of patients (albeit limited) were cases of agranulocytosis. By neuroleptic applies alkaloid plant Rauwolfia serpentina in enth. - P ithout e r n and n. Currently, however, in honors antipsychotic drug, it is used very rarely - only in case of intolerance of all other neuroleptics.

• Prescribe antipsychotics for psychosis (especially with a pronounced impact excitation of, affective reactions, aggression, presence of delusions, hallucinations). Furthermore, they may be useful in the treatment medicament relationship with respect to narcotic analgesics, and ethyl alcohol. The phenothiazines and butyrophenones are also used as anti-emetics and persistent hiccups. The practical significance is its ability to potentiate the effect of neuroleptics funds for drug goat, sleeping pills, narcotic analgesics.

• With long-term use of antipsychotic drugs for the majority of them develop addictive. Drug dependence arises. Antipsychotics are contraindicated or should be used with caution in the pathology of the liver, kidney, cardiovascular disease with symptoms of decompensation in organic diseases General of the nervous system, in violation of hematopoiesis.

• Tranquilizers (anxiolytics) The main groups of substances is an anxiolytic (tranquillizers) and sedative effects. Anxiolytic effect is manifested in the elimination of fear, worry, anxiety, reduced internal stress ¬ him. Tranquilizers are used mainly in neurotic and neurotic (reactive) states. Tranquillizers neuroleptics congestion differ from that for most of them psychosis little or ineffective, the autonomic innervation by main products (except amizila) has no effect, tranquilizers not cause extrapyramidal disorders, seizure threshold increase.

• Sibazon, hlozepida, phenazepam and nozepam have strong anxiolytic and sedative properties. Reducing emotional stress, they also contribute to the onset of sleep. Psychoactive effects of these drugs is mainly attributed to their effect on the limbic system. For example, it is shown that sibazon and analogs largely reduced spontaneous activity of hippocampal neurons than hypothalamus and brainstem reticular formation of the brain. Benzodiazepines also suppress impulsive aftereffect in Limbical system, as well as in the hypothalamus. Apparently, some value has a depressing effect on the reticular activating formation of the brain stem, as benzodiazepines inhibit the reaction EEG activation that occurs on stimulation of the reticular formation.

• The body benzodiazepines react with the so-called benzodiazepine receptors, which are closely related to the GABA receptors. Upon stimulation of benzodiazepine receptor activation is observed GABA receptors. The interaction between the benzodiazepine receptors with the same name appears as a GABA-mimetic effect. One of the most effective tranquilizers is phenazepam. By anxiolytic and hypnotic effects it surpasses sibazon about 5 times. Allocate benzodiazepine anxiolytic action with and no or minimal sedative-hypnotic effect. These drugs are sometimes referred to as "day tranquilizers." These can be classified Medazepam (rudotel).

• Benzodiazepines cause muscle relaxation, which is caused by inhibition of this polysynaptic spinal reflexes and the violation of their supraspinal regulation (such substances are considered among the central governmental muscle relaxants). Benzodiazepines have anticonvulsant ac ¬ ciency. Potentiate the depressant effect on the central nervous system of substances with narcotic type of action. The autonomic Innervation they do not affect (m-anticholinergic, adrenergic blocking properties ganglioblokiruyuschie and they are not available). Blood pressure in the usual therapeutic doses does not change.

• When administered hlozepida and sibazon absorbed quickly nozepam - relatively slow. For the duration of action of a substance can be arranged in the following order: fenazepam> hlozepida> sibazon> nozepam. For fenazepama shown to reduce its blood plasma by 50% occurs in 24-72 hours In the body, benzodiazepines are biotransformation. Meta, conjugates, and small amounts of drugs are derived unchanged in the kidneys, in part - the gastro-intestinal tract. Benzodiazepines are well tolerated. However, in their application may experience side effects: drowsiness, headache, nausea, menstrual disorders, decreased sex on , skin lesion. Chronic administration of benzodiazepines develops addiction, drug dependence may occurence (mental and physical). Similar to the properties of benzodiazepines has derived propanediol - meprotan (meprobamate, andaksin).

• Meprotan well absorbed from the gastrointestinal tract. 1-2 h after administration of plasma observed maximum concentration of a substance that after 10 hours is starting to decline. Meprotan causes the induction of microsomal liver enzymes. Reaction products and the unchanged meprotan allocated advantage considerably in the urine and partly with excrement. By meprotanu develop addiction and drug dependence (physical and mental). When using meprotan may experience drowsiness, lethargy, muscle weakness, allergic reactions, rarely - leukopenia. Significantly different from the groups considered derivative of diphenylmethane - amizil (benaktizin).

• It belongs to the group of central cholinergic antagonists. Its sedative action, obviously, to a certain extent due to the inhibition of M-cholinergic reticular formation of the brain. This is evidenced by the ability to remove the reaction amizila EEG activation induced by holinomimetikami. The EEG has amizil synchronizing effect: there are high-voltage slow oscillations. Amizil increases the effects of substances such as drugs and narcotic analgesics. Has anticonvulsant activity. Suppresses the cough reflex. For amizila also characteristic peripheral m-anticholinergic action (less pronounced than the effect on the central m-cholinergic receptors).

• As a result, it reduces the spasms of smooth muscles, dilates pupils of the eyes, inhibits the secretion of the glands. Furthermore, there amizila anesthetics, antihistaminic and antiserotonin property. Absorbed from the intestine amizil well. Active within a few hours. Excreted in the urine. Side effects are mainly associated with its action atropine (dry mouth, tachycardia, pupillary dilation, etc.). The drug is contraindicated in glaucoma. By tranquilizers are also trioxazine, oksilidin (benzoklidina hydrochloride) and a number of other drugs.

• Tranquilizers are used mainly in the neuroses and the neuroselike states. They are appointed for sedation before Provence surgery. They are widely used for insomnia. Benzodiazepines and meprotan effective in epilepsy, tetanus and other neurological disorders involving skeletal muscle hyper. Persons whose profession requires special attention and fast reaction (eg, transport drivers), appointed outpatient chat tranquilizers should not be.

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