Riboflavin

Riboflavin (Lactoflavin, B2 vitamin) is one of the most important water-soluble vitamins, a coenzyme of many biochemical processes. Riboflavin has bright yellow color and a characteristic vitamin smell.

Riboflavin in sport

Riboflavin participates in formation of energy in three main processes:

• Glucose metabolism
• Oxidation of fats
• Transfer of ions of Hydrogenous in Krebs's cycle

Participation of Riboflavin in synthesis of a protein is of special interest for bodybuilders. There is dependence between entering of Riboflavin in an organism and muscle bulk. One research showed what women need high doses of B2 vitamin, for restoration after the trainings. One more research established that Riboflavin in the form of additional additive improves muscular activity at sports activities therefore it is often included in sports delivery.

Deficiency of Riboflavin

Riboflavin is necessary for formation of erythrocytes, antibodies, for a regulation of body height and genocidal functions in an organism. It is also necessary for a healthy skin, fingernails, body height of hair and in general for health of all organisms, including function of a thyroid gland.

External implications of a failure of Riboflavin at the person are lesions of a mucosa of labium with vertical cracks and an exfoliating of an epithelium (cheilosis), ulcerations in mouth angles (an angular steatites), swelled also reddening of tongue (glossitis), seborrhea dermatitis in nasolabial cord, nose wings, ears, centuries. Often also changes from organs of vision develop: a photophobia, cornea vascularization, conjunctivitis, keratitis and in certain cases is a cataract. In some cases at an avitaminosis the anemia and nervous breakdowns which are shown in muscular delicacy, thermalgias in legs, etc. take place. You can try Cerebramin.

The main reasons for a disadvantage of Riboflavin at the person is insufficient consumption of the products containing this vitamin; the wrong storage and preparation of the products containing this vitamin owing to what the content of vitamin sharply decreases; chronic diseases of digestive tract, reception of medicines, being antagonists of Riboflavin.

Food sources of Riboflavin

Riboflavin contains in the following products (in decreasing order of its quantity in 100 g of a product): liver and kidneys of 2.80-4.66 mg, yeast of 2.07-4.0 mg, almonds of 0.80 mg, eggs of 0.30-0.80 mg, champignons of 0.4 mg, cottage cheese of 0.30-0.50 mg, broccoli of 0.3 mg, white cabbage of 0.25 mg, buckwheat of 0.24 mg, milk of 0.13-0.18 mg, meat of 0.15-0.17 mg, and also: the peeled rice, pasta, white loaf, the majority of fruit and vegetables in number of 0.03-0.05 mg.

Content of B2 vitamin in some foodstuff

Product / Content of B2 vitamin, mg / 100 of a product

Beef liver / 2.19

Yeast baking (pressed) / 2.0

Kidneys / 1.6-2.1

Liver / 1.3-1.6

Cheese / 0.4-0.75

Egg (yolk) / 0.3-0.5

Cottage cheese / 0.3-0.4

Spinach / 0.2-0.3

Veal / 0.23

Beef / 0.2

Buckwheat / 0.2

Milk / 0.14-0.24

Cabbage / 0.025-0.05

Potatoes / 0.08

Salad / 0.8

Carrots / 0.02-0.06

Tomatoes / 0.02-0.04

Recommended doses

The recommended daily dose averages 1.3 mg, for the adult. In case of occupations bodybuilding, requirement increases up to 3-5 mg. Riboflavin has no toxicity and doesn't cause hypervitaminoze in case of the use inside as its low solubility interferes with its excessive absorption from intestines.

Information from the encyclopedia of sport

Riboflavin. At the heart of chemical structure of Riboflavin (Vit. B2) lies system of izoalloksazin. As a side chain its molecule contains remaining balance of pentatonic alcohol of ribitol owing to what vitamin was called Riboflavin.

In a human body Riboflavin arrives mainly with meat and dairy products, it contains also in fish, yeast, peas, germs and covers of cereal cultures.

Medicines: Riboflavin and Riboflavin mononucleotide.

Pharmacokinetics. Riboflavin is absorbed in intestines and is subject to phosphorylation in a mucous membrane of guts, cells of a liver and blood. At the same time two kofermentny forms are formed: flavinmononucleotids (FMN) and flavinadenindinucleotids (FAD).

Riboflavin accumulates mainly in a liver, kidneys and adrenal glands. In fabrics Riboflavin can be in a free condition, however its nucleotides (FMN and FAD) are reliably connected with proteins of an apoferment. Riboflavin from an organism is emitted with kidneys, painting urine in light yellow color.

Pharm dinamics. Riboflavin as prostetic group flavin (yellow) enzymes performs function of a transporter of hydrogen in the course of tissue respiration and regulates oxidation-reduction reactions. Coenzymes of biological oxidation are intermediate carriers of hydrogen from OVER to tsitokhroma, are a part glutathione-reductase enzyme which translates the oxidized glutathione in got into condition.

As a part of oxidase amino acids Riboflavin takes part in synthesis and exchange of amino acids. In general he normalizes exchange of fats and proteins, plays an important role in maintenance of normal visual function of eyes (synthesis of flasks and rods), and participates in function of mucosa’s, skins and in hemoglobin synthesis. Enzymes which incorporate Riboflavin participate in exchange of other vitamins: pantothenic acid, pyridoxine and folic acid. Riboflavin is necessary for coli bacillus vital activity, and also facilitates iron absorption, increases fastness of an organism to hypoxia and other adverse factors.

Riboflavin mononucleotide is a product of phosphorylation of Riboflavin, ready form of coenzyme.

Precursory symptoms of failure of Riboflavin in organism is dysfunctions of CNS (hypochondria, hysteria, depression), decrease further secretion of a gastric juice and activity of enzymes of intestines, appetite worsens, body weight decreases, the feeling of fever in a body appears, there are cracks in angles of a mouth and on labium (an angular stomatitis), tongue becomes dry, bright red color (glossitis), there is an acute pain in eyes, a photophobia, develop keratitis, konyyuktivit, phacoscotasmus (cataract).

Indications to use: hypo - and ariboflavinosis, diseases of eyes (keratitis, konyyuktivit, helcomas, cataract) and skins (seborrheal eczema, a systemic lupus erythematosus), combustions, a frostbite, a myocardial dystrophy, chronic enteritis, radial illness, failure albuminous and excessive carbohydrate deliveries.

Riboflavin the mononucleotide is used in ophthalmology, dermatology, neurology.

Side effects are observed at over dosage. Riboflavin the mononucleotide causes morbidity in injection site. Treatment by high doses of vitamin owing to its bad solubility can cause an occlusion of canaliculus of nephron.

Riboflavin (B2 vitamin drug). Investigated influence of additional consumption of Riboflavin on physical efficiency of 14 Canadian swimmers of high qualification with the normal status for this vitamin and the regimen of its consumption with a nutrition meeting the recommended standards. Surveyed one subgroup for 16 — 20 days accepted it in a dose of 60 mg a day whereas for surveyed other subgroup drug replaced placebo. Physical working capacity was estimated in the swimming test consisting in sixfold overcoming 50-meter distance freestyle. Besides, in the tredmilny test defined the maximum aerobic power and a ventilating anaerobic threshold. Drug considerably increases visual acuity and fastness to a hypoxia; at the same time consumption of Riboflavin in long tests didn't affect indicators of its level in a blood, on indicators of physical working capacity. The conclusion was drawn that in the course of the sports training swimmers completely can support the normal riboflavin status without additional consumption of this vitamin. Besides, it is obvious, it is necessary to fulfill its dosages for the athletes specializing in firing and also in other sports, taking into account anti-hypoxemic effect.

B2 vitamin in itself has no anabolic activity, and its forms Riboflavin a mononucleotide and Flavinatum which in Ukraine aren't issued — possess. Drugs activate the enzymes participating in synthesis of amino acids, lipids and carbohydrates. They normalize the course of oxidation-reduction processes, cholesterol exchange, strengthen hemoglobin synthesis, accelerate iron absorption, and improve vision. For the growing organism these drugs are an irreplaceable growth factor.

Action mechanism of G - squirrels - the connected receptors

The mechanism of signal transmission is identical at all G squirrels - the connected receptors (And). After accession of receptor conformation changes. Subjedinitsa gives GDF and attaches GTF, then separates from two other subjedinitsa, comes into contact with effector protein and changes his functional state. And β, and at-subjedinitsy are capable to contact effector proteins. a-Subjedinitsa provides slow hydrolysis of the connected GTF to GDF. Ga-GDF has no affinity to effector proteins and again reunites with β, at-subjedinitsami (And).

G-proteins can diffundirovat (lateralno) in a membrane; they aren't connected with a certain type of receptors. Nevertheless between types of receptors and types of G-proteins there is an interrelation (B). a-Subjedinitsy G-proteins differ on affinity and type of impact on effector proteins. Ga-GTF Gg-áåëêà stimulates to an adenilattsik-manhole while Ga-GTF Gj-áåëêà inhibits it. To G - protein - to the connected receptors muskarin holinoretseptor, receptors belong to noradrenaline, adrenaline, a dopamine, a histamine, morphine, prostaglandins, leykotriyena and other substances and hormones.

Effector proteins for G-protein are an adenilattsiklaza (ATP - an intracellular carrier of tsAMF), a phospholipase With (fosfatidilinozitol, intracellular carriers inozitoltrifosfat and diacylglycerin) and some proteins of ion channels (B).

The set of functions as tsAMF increases activity of a protein kinase And which fosforilirut regulatory proteins depends on concentration of tsAMF in a cell. Besides, rising of concentration of tsAMF leads to relaxation of a smooth musculation, rising of force of cordial reductions, intensifying of glycogenolysis and lipolysis. Phosphorylation of proteins of Sa-channels promotes their opening at depolarization of a membrane. It is necessary to notice that tsAMF is inactivated by phosphodiesterase. Therefore inhibitors of this enzyme maintain high cellular concentration of tsAMF and have effect, similar to an adrenaline.

Besides, receptor protein can fosforilirovatsya and thereof loses ability to activate G-protein. This mechanism is the cornerstone of depression of sensitivity of a cell as a result of long stimulation of a receptor under the influence of an agonist.

Activation of phospholipase With leads to splitting of phospholipids of membranes (fosfatidilinozitol-4.5-bifosfata) with formation of inozitoltrifosfat (1P3) and diacyl of Glycerinum (DAG). Inozitol stimulates an exit of Sa2 + from depot that leads to reduction of a smooth musculation, splitting of a glycogen or an exocytosis. Diatsilglitserin stimulates a protein kinase With which fosforilirut defined a serine - and the threoninecontaining enzymes.

Some G-proteins influence proteins of channels and promote opening of channels. Thus are activated by K+ - channels (action of Acetylcholinum at the synoptic level; influence of opioids on transfer of exaltation in nervous cells).

Systems of the secondary messengers connected to G-proteins.

In the table examples of similar receptor systems are given. It is obvious that a large number of primary messengers is regulated some by secondary. Thus, it is necessary to understand that specificity of action of initially communicating ligands is defined by localization of a receptor on certain cells in which secondary messengers cause an expression of the proteins specific to this cell.

Receptors connected to G-proteins

More than 1000 genes encoding the receptors connected to G-proteins are opened. These receptors are monomeric glycoproteins with rather similar amino-acid composition. 7 domains having hydrophobic amino acids as a part of a polypeptide circuit are characteristic of them. These domains are formed by loops in a diaphragm with one end which is coming out, and another - in cytoplasm.

Endogenous ligands communicate on an external section of a receptor. Small by the size, for example amines, join sections in different transmembrane areas whereas large, for example the polypeptides less capable to penetrate into hydrophobic regions communicate on ecstracletoc loop of a N-end section of a receptor. You can also like Cerebramin.

G-squirrels join an intracellular segment of a receptor in the 3rd loop between the 5th and 6th regions. Though the mechanism of the effect arising at connection with agonist isn't up to the end clear, it is supposed that this act stabilizes a receptor in the conformation allowing him to interact with the trimmer of G-proteins, activating them and the subsequent effector events.

The effect of agonist usually has only limited duration that is defined by several processes. The majority connected with G-proteins and receptors Cerina and a treonina in cytoplasmatic loop and in the S-trailer site which can be several kinases that limit interaction between a receptor and G-protein has the remains. This process is called desensitization of a receptor and allows a cage to answer very wide ranges of the concentration stimulating of agents. After long influence of agonist the number of receptors on a plasmatic membrane can be also regulated by the internalization process (which is carried out in certain cases by a catabolism), or down-regulation of a receptor. Though the signals causing her aren't clear, it is represented that they are excellent from controlling desensitization.

G-proteins

Carry out transduction of a signal from membrane receptors to effectors enzymes and ion channels. Each of these proteins consists of three separate subunit designated α, β at as decrease in molecular weight; the α- subunit of the trimmer and is the chief intermediary of influence of G-proteins on their effector. The main function β-and γ-subunit of the trimmer is support of interaction of a α- subunit with a plasmatic membrane and receptors, however they are capable also to direct regulation of effector.

Families of G-proteins mammals

The G-squirrels participating in transmembrane transfer of a signal are regulated by the general mechanisms. In the drawing their cycle of activation and an inactivation is presented. In a basal state three subunit of G-proteins are connected together and with guanozindifosfat (GDF), attached to α- subunit. When agonist connects to a receptor, GDF separates, and the place freed on α- subunit is taken guanozintrifosfat (GTF), a lot of present at cytoplasm.

Emergence of this communication stimulates G-proteins, as a result of α- subunits separate from a receptor and from β, γ- subunit and contacts effector. Several seconds later Gtfaza who is available in α- subunit hydrolyzes the connected GTF to GDF that leads to an inactivation of subunit. The α- subunit connected with GDF separates from effector and again is associated with β-, a γ-complex of G-proteins of G-proteins, becoming capable to a new cycle of activation by receptor.

The functional distinctions between members of family of G-proteins initially are defined by differences in the α- subunits. The nomenclature of G-proteins was initially built according to their function. So, the designations Gs and Gi are accepted for the G-proteins stimulating and inhibiting respectively. The designation Gi was entered earlier when for the first time the G-protein discovered in a retina was called transdutsin.

Imperfection of this nomenclature became obvious after separation and cloning of G-proteins with the obscure function. So there were designations Go, Gq, then G11, G12, etc. Some G-proteins expressed only in certain types of cells, for example Gt is found only in sticks and cones of a retina where activates a tsGMF-specific fosfodiesteraza. Other G-proteins, on the contrary, in the majority of fabrics and have multiple function, for example, Gi is present at the majority of cells, inhibiting, but is capable also to direct impact on some ion channels.

The influence of the majority of G-proteins on effectors is stimulating however some inhibit them. For example, G0 inhibits Sa2+-channels in a brain and heart; Gs stimulate, a Gi inhibits. The last two G-proteins are in turn regulated by different groups of receptors which are often provided in one cell. Result of simultaneous activation of the stimulating and inhibiting receptors is reduction and mitigation of response.

This double regulation in addition to interaction of other following behind proteins of components of signal system provides the integrated response of a cell to numerous incentives.

Effector enzymes regulated by G-proteins. From three components providing the carrying out a signal interfaced to G-proteins, it is the most difficult to study effector links at the molecular level. Only recently some of enzymes of this link were isolated and cloned.

Effects hormonal and receptors most often are implemented through adenilattsiklaza and phospholipase of Page. Other enzymes, such as A2 phospholipase producing arakhidon acid also, apparently, are regulated by G-proteins, however these responses are up to the end not clear.

Adenilattsiklaza and tsAMF as a secondary messenger

Cyclic AMF (tsAMF) is synthesized from ATP by adenililtsiklaz enzymes which are built in a plasmatic diaphragm.

It is represented that these enzymes are the big polypeptides containing two clusters from six transmembrane segments separating two similar catalytic domains. Is available, on extreme a Mercedes, eight forms of adenilattsiklaza. All of them are stimulated with Gsα, but differ on sensitivity to the inhibiting influence of Gα-stimulation in calmodulin (calcium/calmodulin) and on effect β, at-subunits G-proteins. These additional regulators give ability to integrate many signals influencing different systems of secondary in one cell.

Cyclic AMF shows the effect in a cage, generally activating tsAMF-dependent proteinkinaza (a proteinkinaz of A, PKA). These tetrameasured enzymes consist of two regulatory and two catalytic subjedinitsa. Enzymes are activated when two molecules tsAMF join each regulatory subunits, releasing catalytic subunits from tetrameasure. The released subunits catalyze transfer of phosphatic group of ATP on the specific serinov or treaninon remains of proteins targets. Among them there can be enzymes which participate in metabolic processes of cage, and the proteins regulating a gene transcription. The metabolic way activated by tsAMF making the cascade of enzymatic activation leading to disintegration of a glycogen in liver is well studied, for example. The activated proteinkinaza and fosforilirut fosforilazny kinase (phosphorylase kinase) which in turn fosforilirut glikogenfosforilaza is enzyme catalyzing disintegration of glycogen.

Action of tsAMF on a transcription of genes is mediated catalyzed protein and phosphorylation of the protein known under the name cAMP response clement-binding protein (CREB) which joins the specific short sequences of DNA known as cAMP response elements (CRE). CREB joins CRE, being fosforilirovan and that stimulates a transcription of the genes supporting CRE in regulatory zones.

Phospholipase with and phospholipid secondary messengers

Representatives of family of G-proteins integrate various receptors to group of the enzymes famous as phospholipases cf. These enzymes concern to big family of phospholipases for which substratum are inozitolfosfolipida. The alarm transduction in this way attracts the sequence of molecular events similar with observed in case of activation of an adeiilattsiklaza. Linkng of agonist with a receptor activates G-protein which in turn joins a phospholipase on an internal surface of a plasmatic membrane. The activated lipase quickly turns fosfatidilinozitolbifosfat (PIP2) in inozitoltrifosfat (IP3) and diatsilglitserol. Both of these molecules work as secondary messengers in two various ways: IP3 the small water-soluble molecule capable to diffundir quickly in cytoplasm and to join 1RZ-dependent calcic channels in a smooth endoplasmic retikulum, releasing calcium inventories in cytosol.

Increase in concentration of Sa2 + in cytoplasm initiates a wave of Sa2+ reactions in a cage, many of them are mediated by specific Sa2+ proteins from which the calmodulin is most widespread. Sa2+-kalmodulin regulates a number of enzymes, including Sa2+-zavisimuyu to ATFAZ of a plasmatic membrane which extorts calcium from a cage, and as it was told earlier, some types of adeiilattsiklaza. The majority of effects of calcium in a cage is result of activation of group proteinkinaz, known as Sa2+-calcium module depending proteinkinaza. These kinases fosforilirut seri-new and treonin remaining balance of various proteins. Thus, again physiological response to activation of phospholipid secondary messenger in each cage depends from ekspres in it the proteins which are target Sa2+.

Other molecular product of hydrolysis of PIP2 a phospholipase With is äèàöèëãëèöåðîë. This lipidic molecule remains in a plasmatic diaphragm where together with fosfatidilseriny the serin-treoninovykh êèïàç, known as a proteinkinaza of Page activates some members of other family. These soluble kinases peremetatsya in a diaphragm in response to increase in calcium in ïè ãî to a spinning top (IP3 caused by release) and then are activated by combined influence of Sa2 + a diatsilglitserola and a fosfatidilserina. Being activated, these kinases fosforilirut groups, specific to a cell, the substratnykh of proteins which include many ion channels, receptors and other kinases that as a result increases a gene transcription.

Other processes of signal transduction regulated by G-proteins. In addition to the described enzymes it was shown quite recently that G-proteins modulate also activity voltazh depending ion channels. Apparently from the table, many hormones and neurotransmitters regulate both secondary messengers, and the ion channels, activating one G-protein. In particular, Gt stimulates both adenilattsiklaza, and some types of Sa2+-channels.

Obviously, further clearing up of mechanisms of direct and reverse regulation of receptor systems of a signal transduction is one of the most important scientific tasks of the future.

Bromazepam - Active Substances. Instruction and Application, Dosage

Name: Bromazepam

The Latin name of the substance Bromazepam

Bromazepamum (genus Bromazepami)

Chemical name: 7-Bromo-1,3-dihydro-5- (2-pyridinyl) -2H-1,4-benzodiazepin-2-one

Formula - C14H10BrN3O

Therapeutic substances Bromazepam - anxiolytics

The nosological classification (ICD-10)

F20 Schizophrenia
F39 Upset Mood [affective] unspecified
F41 Other anxiety disorders
R45.1 Restlessness and agitation

CAS code - 1812-30-2

Characteristics substance Bromazepam

Anxiolytic, benzodiazepine derivative.

Pharmacology of Bromazepam

Mode of action - anxiolytic, sedative.

It stimulates GABA receptors ascending activating reticular formation. It increases the braking effect of GABA in the central nervous system, enhances the effects of endogenous GABA, reduces the excitability of the cortex and the limbic system of the brain, slows polysynaptic spinal reflexes. Reduces tension and anxiety in large doses have a sedative and central muscle relaxant effect. It reduces emotional tension, anxiety, fear, anxiety, reduces the neurotic symptoms.

After ingestion blood Cmax is reached within 2 hours. The bioavailability of the tablet form is 60%. Linking blood protein is 70%. The volume of distribution - 50 liters. In repeated dose equilibrium concentration in the blood is normally achieved within 2-3 days. Treated microsomal oxidation (N-dealkylation, aliphatic hydroxylation) to form a 3-gidroksibromazepama and 2- (2-amino-5-bromo-3-hydroxybenzoyl) pyridine, and their glucuronides. T1 / 2 - 20 hours may be increased in elderly patients. Write mainly in the urine as conjugated metabolites (2% unchanged). Clearance of the drug is 40 ml / min. Accumulation at the re-appointment of the minimum.

Application of the Bromazepam substance

Alarm syndrome, including state of anxiety and tension, somatic complaints; anxiety and excitement in mental illness, including in affective disorders, schizophrenia (in combination therapy).

Contraindications of Bromazepam

Hypersensitivity (including to other benzodiazepines), cerebral and spinal ataxia, suicidal tendencies, angle-closure glaucoma; hypercapnia; severe respiratory distress, apnea during sleep; liver failure; myasthenia gravis; drug or alcohol (except for acute withdrawal) dependence, pregnancy, breast-feeding.

Restrictions to application

Age 18 years (safety and efficacy of the children are not identified).

Pregnancy and breast-feeding
Contraindicated during pregnancy. At the time of treatment should stop breastfeeding.

Side effects of Bromazepam substance 

From the nervous system and sensory organs: headache, dizziness, weakness, fatigue, drowsiness, mental retardation and motor responses, blunting of emotions, impaired concentration, ataxia, tremors, muscle weakness, diplopia, dysarthria, confusion, anterograde amnesia (with concomitant inappropriate behavior), a manifestation of latent depression, paradoxical reactions (restlessness, agitation, anxiety, irritability, aggressiveness, delusions, rage, sleep disturbances, nightmares, hallucinations, psychosis, inappropriate behavior).

From the digestive tract: nausea, dry mouth, excessive salivation, constipation, increased activity of hepatic transaminases and alkaline phosphatase, jaundice.

Other: urinary incontinence, skin rash, changes in libido.

Perhaps the development of drug dependence, withdrawal syndrome, rebound-a syndrome

Interaction of Bromazepam

Effect increase neuroleptics al. Anxiolytics, tricyclic antidepressants, hypnotics, sedatives and anticonvulsants, narcotic analgesics, anesthetics, antihypertensives, muscle relaxants, antihistamines with sedative properties alcohol. Carbamazepine, cimetidine, inhibitors of microsomal enzymes increase the T1 / 2. Reduces the therapeutic effect of levodopa. Increases toxicity of zidovudine.

Overdose of Bromazepam

Symptoms: oppression CNS varying degrees of symptoms (from somnolence to coma), in mild cases - drowsiness, confusion, lethargy; in more serious cases (especially in patients receiving other drugs which depress the central nervous system, including alcohol) - ataxia, areflexia, hypotension, respiratory depression and cardiac (up to respiratory arrest) activity, coma; rarely - death.

Treatment: gastric lavage, induction of vomiting, the appointment of activated carbon, respiration monitors, heart rate, blood pressure, maintain cardiovascular activity, and airway management, in / in a liquid. In the event of hypotension - in / in the introduction of dopamine, norepinephrine. As a specific antidote used BZ antagonist flumazenil receptors (in the hospital).

Dosing and Administration of Bromazepam

Inside. The mode set is strictly individual, the average dose for adults in outpatient treatment: at 1.5-3 mg 2-3 times a day; if necessary (in the hospital) increase the dose to 6-12 mg 2-3 times a day. Children older than 1 year (if applicable) the dose selected individually depending on body weight. Patients are elderly, debilitated patients, and patients with impaired liver function should be prescribed lower doses. The total duration of treatment - no more than 8-12 weeks, including the period of gradual dose reduction; continued treatment beyond this period is possible only after a careful assessment of the patient's condition.

Precautions substance Bromazepam
There should be appointed for the monotherapy of depression, including anxious depression, due to the possibility of suicide. Paradoxical reactions are more common in children and elderly patients. In the event of paradoxical reactions bromazepam should be abolished. It is recommended to reduce the dose gradually, as the risk of withdrawal symptoms above in a sharp lifting of the drug.

When receiving bromazepam (even at therapeutic doses) may develop physical and psychological dependence. Depending risk increases when large doses and with increasing duration of the reception, as well as in patients with alcohol dependence and drug history. Abolition of bromazepam should be done gradually by reducing the dose to reduce the risk of withdrawal symptoms and rebound-a syndrome. In abrupt cancellation after long-term use or high doses there is a withdrawal syndrome (headache and muscle pain, agitation, anxiety, confusion, tremors, convulsions), in severe cases - depersonalization, hallucinations, seizures (sudden elimination in epilepsy). Transient syndrome where symptoms giving rise to the appointment of bromazepam, resumed in a more pronounced form (rebound-Syndrome), may also be accompanied by mood changes, sleep disturbance, anxiety and others.

Benzodiazepines may cause anterograde amnesia, which develops when using doses close to the upper limit of therapeutic range (for documented bromazepam 6 mg dose), at higher dosage increases her risk.

With long-term treatment requires monitoring of liver enzymes. Should not be used during the drivers of vehicles and people, a profession which requires high concentration of attention. In the period of treatment is unacceptable consumption of alcoholic beverages.

Special instructions for Bromazepam
At the time of treatment should abandon admission alcohol.

Trading names of drugs with Bromazepam working substanceTrade Name Index

Bromazepam, Bromazepam Lannaher, Bromide, Lexotan

Fabomotizole - Active Substances. Instruction and Application, Dosage

Name: Fabomotizole

The Latin name of the substance Fabomotizole

Fabomotizolum (genus Fabomotizoli)

Formula - C15H21N3O2S

Therapeutic substances Tofisopam- anxiolytics

The nosological classification (ICD-10)

F10.3 abstinence
F10.4 abstinent state with delirium
F11 Mental and behavioral disorders due to use of opioids
F32.0 Depressive episode mild
F40.2 Specific (isolated) phobias
F41.1 Generalized anxiety disorder
F43.1 Post-traumatic stress disorder
F43.2 Disorder adaptive reactions
F45 Somatoform disorders
F48 Other neurotic disorders
F60.3 Emotionally unstable personality disorder
N94.3 syndrome premenstrual tension
N95.1 menopausal and menopausal status of women
R07.2 Pain in the heart

CAS code - 173352-39-1

Pharmacology

Mode of action - anxiolytic.

Application of the substance Fabomotizole

Neuroses and neurosis-like states; State, accompanied by emotional stress, autonomic disorders, moderate, fear, apathy, decreased activity, intrusive experiences; reactive depression with moderately severe psychopathological symptoms; post-traumatic stress disorder; disorder mental adaptation; cardiology (monotherapy or in combination with other drugs), climacteric syndrome (monotherapy and in combination with hormonal therapy); premenstrual stress syndrome; myasthenia gravis, myopathies, neurogenic muscle atrophy and other pathological states with secondary neurotic symptoms when anxiolytics contraindicated with pronounced muscle relaxant effect.

Trading names of drugs with Fabomotizole working substance

Trade Name Index 

Afobazol, Afobazole

Modern studies of Amyotrophic lateral sclerosis

Neurologist Dr. Doping tells about corpuscles Bunin, the impact of stress on neurons and gene mutation in neurodegenerative diseases.

Amyotrophic lateral sclerosis - a severe neurological disease that is characterized by progressive loss of neurons responsible for movement and thought processes. It manifested it gradual muscle weakness. The person loses the ability to move his arms, legs, impaired breathing and speech. A few words about the history of this disease. The first description of the structure of motor and sensory waves that come within the nervous system, was done in the 30s of the XVIII century, when Magendie described this division. Until now, it is a fundamental principle of the anatomy of the nervous system.

n the future, it has been described by a number of cases where the death of nerve cells caused muscle weakness, atrophy and paralysis in humans. In those days it was not obvious that the weakness may be caused by damage to the nervous system at different levels: at the nerve cell level in the brain, spinal cord, peripheral nerve cells, and therefore those descriptions, which combined clinical and anatomical studies have been published and widely discussed. As a result, all the glory from the description of ALS as the disease got famous neurologist Charcot, who in 1874 identified the disease as an independent unit, and said that progressive muscular paralysis with atrophy caused by the death of nerve cells in the brain and spinal cord, are called amyotrophic lateral sclerosis. Now it is his description. Kozhevnikov The first description was made in Russia in 1883. Important national contribution to the study of this disease was to describe the so-called cells Bunin - is oxyphilous activate nerve cells - in 1962. These inclusions are still studied and described in all textbooks - both domestic and international - under the eponym "Bunin calf."

Interestingly, in the definition of the disease appear the word that is the death of cells responsible for movement. In fact, if you deeply understand the problem, it is not about individual cells, but the cells of the system. Even Charcot suggested that, having been born in one part of the nervous system, the disease is spreading in several of its departments. Then we necropsy found that the characteristic intracellular inclusions formed neurons in the motor cells, and the cells of the frontal lobe, responsible for planning actions for thinking. Then clinical descriptions have confirmed that these people are memory disorders - not only for the movement responsible damaged elements of the nervous system. Then geneticists have shown that the same mutations can lead some people to the movement disorders, while others - the memory disorders. Then came the researchers, who tied it into a kind of evolutionary theory and said that the BAS system are damaged, which has consistently developed in the framework of evolution, namely responsible for the grasping hand movements, walking upright, speaking and socializing.

To improve brain functions use Cogitum, Semax, Noopept, Phenylpiracetam.

Traditionally, the mechanisms that are responsible for the emergence and development of the disease include toxicity, oxidative stress, disturbance of axonal transport, a lack of neurotrophic factors. But nevertheless it is still not entirely clear why the disease develops in adulthood. Why do some patients with the same mutation in the disease appears, and the disease does not develop their relatives? In 2014 he published an article that analyzed quite common known epidemiological data and made the assumption that the ALS is a multistep process. To people sick, you need to go through 6 stages. This means that the mechanism of disease, each of these mechanisms play a role, but it can not run on their own process. This greatly complicates the study when it is necessary in some human populations to identify not just one factor that leads monogenic disease, and when it is necessary to identify the presence of a combination of this gene with certain environmental factors. Nevertheless, these factors continue to be studied. For environmental factors include smoking, physical activity, injury, participation in armed conflicts, pesticides, some others. As for genetic factors that are considered launchers in this disease, they are known to date, approximately 10% of all people who suffer from this disease. We can talk about 20-25 genes that increase the predisposition of the disease. Four of them are the most common: the SOD1 gene, first open in this disease, TDP43 gene, and the FUS gene C9orf72 gene, which was opened in 2011 and has led to a rethinking of the mechanisms of this disease.

Now we will talk about how to change our understanding of the mechanisms of development of the disease after the discovery of mutations in the gene C9orf72. Mutation of this hidden due to the fact that it is located in the intron of the gene. And this mutation refers to the expansion of the hexa-nucleotide repeats, ie, needed specific genetic methods to detect this mutation. How does it work? Apparently, due its pathological effect in that on the basis of DNA in which an excess amount of hexa-nucleotide repeats accumulates to a few thousand as compared with 20 normal, several thousands of repetitions, that is, words that are recorded within the genome correctly but they obsessively repeated. The result is an excess portion of the RNA that does not encode any protein. Why think so? Because there is no so-called start-codon, which begins with the protein translation.

But it turned out that there is a mechanism by which the protein can be broadcast in the absence of the start codon. The result is a protein consisting of the b-peptides which may be toxic and in this disease. What can these proteins? They are formed in the cytoplasm and bind to RNA, which is also in the cytoplasm are located there for the translation process. As a result of impaired interaction with other proteins of RNA. Critical, apparently, it becomes in a stressful situation, because it is known that in neurons under stress - asthmatic stress or stress in the form of increased temperature or oxidative stress - the stress granules are formed. This aggregation link RNA to proteins. These proteins with prion sequences protect RNA from degradation by proteases, making it more resistant to stress. Then the stress granules at the end of the stress decay, and extend all the processes associated with the formation of proteins, RNA transport.

So, these bi-peptide proteins that are produced in excess RNA, blocking the dynamics of stress granules, and do not break after the stress is finished. As a result, they accumulate within the cytoplasm of cells, and they contain a variety of proteins. All this repeatedly confirmed histologically. These are the inclusions that are typical for this disease. What do we get? Neuron affected by stress, can not be restored - this is the first problem, that is, can not go on the formation of proteins from RNA. The second problem - when proteolysis resistant accumulate inside the cell clusters, which include various RNA proteins, and this in turn triggers a series of pathological processes.

Modern research to find treatments focused on the processes associated with the formation of a bi-peptide proteins, ie they block the pathological broadcast. They just stop it with the C9orf72 gene. It is known that a complete blockade of the formation of this protein is not lethal to cells and, as shown by experiments, slows down or completely stop the disease in animals that have this mutation, and without such a treatment would be sick bass, but with treatment, this process stops. On the basis of these studies, carried out a search for new disease markers, because there is a search for methods of these bi-peptide proteins in the cerebrospinal fluid. This marker can be used both for diagnosis and for monitoring treatment of disease. If the amount of treatment by the action of the bi-peptide proteins decreases, then the treatment is effective. This makes it possible to accelerate clinical research.

Now one of the basic models of disease - a model for pluripotent stem cells, when the patient ALS mutation C9orf72 taken, for example, fibroblast, i.e. a piece of skin, and is under the influence of special factors converted into neurons, which also suffer from his own neurons. And research on these neurons allow to accelerate new drug discovery process as we can test drugs in much larger quantities and much faster than we could do it on a human. That is, the discovery of this mutation has allowed us to move forward in the development of models of disease and in the development of markers for the diagnosis and monitoring of treatment and the search for new treatments for themselves. And it confirmed the existence of a relatively new and newly discovered mechanisms of broadcasting without a start codon. Science has made thanks to the disease a significant step forward, and we hope that it will be effective in relation to drug discovery.

Tofisopam - Active Substances. Instruction and Application, Dosage

Name: Tofisopam

The Latin name of the substance Tofisopam

Tofisopamum (genus Tofisopami)

Chemical name: 1- (3,4-dimethoxyphenyl) -5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine

Formula - C22H26N2O4

Therapeutic substances Tofisopam- anxiolytics

The nosological classification (ICD-10)

F10.3 abstinence
F10.4 abstinent state with delirium
F11 Mental and behavioral disorders due to use of opioids
F32.0 Depressive episode mild
F40.2 Specific (isolated) phobias
F41.1 Generalized anxiety disorder
F43.1 Post-traumatic stress disorder
F43.2 Disorder adaptive reactions
F45 Somatoform disorders
F48 Other neurotic disorders
F60.3 Emotionally unstable personality disorder
N94.3 syndrome premenstrual tension
N95.1 menopausal and menopausal status of women
R07.2 Pain in the heart

CAS code - 22345-47-7

Characteristics substance Tofisopam
"Full-time" antianxiety drug, an atypical benzodiazepine derivative (2,3-benzodiazepine). White to yellowish white crystalline powder. Practically insoluble in water, soluble in alcohol difficult.

Pharmacology

Mode of action - anxiolytic.

Interacts with benzodiazepine receptors increases the sensitivity of the GABA neurotransmitter-receptor enhances GABA-mimetic processes in the CNS. It has anxiolytic activity, accompanied by virtually no sedative, muscle relaxant and anticonvulsant properties. Has vegetative stabilizing and stress-protective effect, dilates coronary vessels. Especially effective for physical symptoms of anxiety.

When administered is rapidly and almost completely absorbed from the gastrointestinal tract, Cmax in the blood is reached within 2 hours after the plasma concentration decreased monoexponential. T1 / 2 6-8 h, the biotransformation products formed have no anxiolytic effect. Write mainly in the urine (60-80%) in the form of glucuronide, 20-30% is excreted in the faeces. Not accumulates.

Application of the substance Tofisopam

Neuroses and neurosis-like states; State, accompanied by emotional stress, autonomic disorders, moderate, fear, apathy, decreased activity, intrusive experiences; reactive depression with moderately severe psychopathological symptoms; post-traumatic stress disorder; disorder mental adaptation; cardiology (monotherapy or in combination with other drugs), climacteric syndrome (monotherapy and in combination with hormonal therapy); premenstrual stress syndrome; myasthenia gravis, myopathies, neurogenic muscle atrophy and other pathological states with secondary neurotic symptoms when anxiolytics contraindicated with pronounced muscle relaxant effect.

The Addictions: alcohol withdrawal syndrome, delirious state (for de-excitation and vegetative symptoms), opium withdrawal syndrome and post-abstinent state. Neurotic, psychotic disorders with alcoholism, as well as conditions characterized by apathy, decreased activity in alcoholism.

Contraindications

Hypersensitivity (including to other benzodiazepines), psychosis and psychopathy with pronounced psychomotor agitation, aggressiveness or deep depression; decompensated respiratory failure, apnea syndrome during sleep (in history), the simultaneous application of tacrolimus, sirolimus, cyclosporine; pregnancy (I term), breast-feeding, age under 18 years.

Restrictions of application of Tofisopam

Decompensated chronic respiratory distress syndrome, acute respiratory failure in the history of angle-closure glaucoma, epilepsy, organic brain damage (such as atherosclerosis).

Side effects of Tofisopam substance 

From the nervous system and sensory organs: headache, agitation, irritability, aggressiveness, irritability, sleep disorder; sometimes - confusion, seizures in patients with epilepsy.

From the respiratory system: respiratory depression.

From the digestive tract: loss of appetite, nausea, dry mouth, gastralgia, dyspepsia, increased separation of gas, constipation; in some cases - congestive jaundice.

From the musculoskeletal system: muscle tension, muscle pain.

Allergic reactions: itching, rash.

Interaction

It contraindicated Tofisopam combined use with tacrolimus, sirolimus, cyclosporine. Hepatic enzyme inducers (alcohol, nicotine, barbiturates, antiepileptics) Tofisopam may enhance metabolism, which may lead to a decrease in its plasma concentration and therapeutic effect of weakening.

Some antifungal drugs (ketoconazole, itraconazole) may slow Tofisopam hepatic metabolism, which leads to an increase in its concentration in plasma. Some antihypertensives (clonidine, BPC) may enhance the effects Tofisopam.

Together with the admission Tofisopam may increase plasma levels of drugs that are metabolized by CYP3A4.

Overdose of Tofisopam

Symptoms: deep sleep, in severe cases (after receiving doses of 50-120 mg / kg) - vomiting, confusion, coma, respiratory depression and / or seizures.

Treatment: restoration of function of respiration and cardiovascular activity.

Dosing and Administration of Tofisopam

Inside. The mode set individually, depending on the indication, the patient's condition, drug tolerability. Single dose - 50-100 mg, the daily average - 150-300 mg 1-3 reception, the maximum - 300 mg / day for 4-12 weeks, including the time of gradual withdrawal of the drug. In the elderly and patients with renal insufficiency dose reduced by 2 times.

Precautions substance Tofisopam
When an allergic reaction or severe sleep disorders should be discontinued. For the prevention of sleep disorders is recommended to take the drug last time no later than 15-16 hours.

It should be noted that patients with mental retardation, elderly patients, as well as having disorders of the kidneys and / or liver disease, are more likely than other patients may experience side effects.

Not recommended for use Tofisopam with chronic psychosis, phobias or obsessive-compulsive disorder. In these cases, the risk of suicide attempts and aggressive behavior. Therefore Tofisopam not recommended as monotherapy depression or depression accompanied by anxiety.

Care should be taken when treating patients with depersonalization, and organic brain damage (such as atherosclerosis). Permanent medical supervision is required when administered to patients with myasthenia gravis.

In patients with epilepsy Tofisopam may increase the seizure threshold.

Tofisopam does not significantly reduce the ability to concentrate. The question of the means of transport management capabilities solved after assessing the patient's individual response to the drug.

Trading names of drugs with Tofisopam working substance

Trade Name Index 

Grandaxin, Tofisopam

Proxibarbal - Active Substances. Instruction and Application, Dosage

Name: Proxibarbal

The Latin name of the substance Proxibarbal

Proxibarbalum (genus Proxibarbali)

Chemical name: 5- (2-hydroxypropyl) -5- (2-propenyl) -2,4,6 (1H, 3H, 5H) -pyrimidinetrione

Formula - C10H14N2O4

Therapeutic substances Proxibarbal - anxiolytics

The nosological classification (ICD-10)

G43 Migraine
K25 Gastric ulcer
K26 Duodenal Ulcer
N94.3 syndrome premenstrual tension
N95.1 menopausal and menopausal status of women
R51 Headache

CAS code - 2537-29-3

Characteristics substance Proxibarbal
The white crystalline powder and odorless. Slightly soluble in water, soluble in alcohol, ether, chloroform and methylene chloride.

PharmacologyMode of action - a sedative, tranquilizing.

It regulates the function of the reticular formation, the hypothalamus and the autonomic nervous system. It inhibits the action of neurotransmitters excitement intensifies the effects of GABA. Reduces neurovegetative disorders accompanying psychosomatic disorders. It eliminates anxiety, restlessness, irritability, vasomotor headache (including migraine). It has a regulating effect with autonomic dysfunction. Stabilizing effect on the CNS after 4-10 days after initiation of therapy.

When ingestion rapidly and completely absorbed from the gastrointestinal tract. Cmah reached after 30 minutes. Easily it passes through the blood-tissue barriers, including GEB. It is metabolized in the liver. Report mostly kidneys.

Application of the substance Proxibarbal

Headache vasomotor origin, migraine, neurosis, psychopathy, vegetative lability somatic disorders, premenstrual syndrome, menopausal disorders, gastric ulcer and duodenal ulcer (in the complex therapy).

Contraindications

Hypersensitivity, kidney and liver failure, pregnancy, breast-feeding.

Restrictions of application of Proxibarbal

Children under 18 years of age (safety and efficacy have not been determined).

Pregnancy and breast-feeding
Contraindicated during pregnancy. At the time of treatment should stop breastfeeding.

Side effects of Proxibarbal substance 

Dizziness, somnolence, dyspepsia, allergic reactions; long-term use - addiction and drug dependence.

Interaction

It enhances the effects of (each) other sedatives (including alcohol).

Overdose of Proxibarbal

In case of overdose possible drowsiness.

Dosing and Administration of Proxibarbal

Inside, 50-100 mg 3 times a day for 4-6 weeks.

Precautions substance Proxibarbal
Be wary appoint elderly and debilitated patients, children with depression. It should not be used in combination with other drugs sedatives.

Should not be used during the drivers of vehicles and people skills relate to the high concentration of attention.

Trading names of drugs with Proxibarbal working substance

Trade Name Index 

Ipronal

Ethylmethylhydroxypyridine succinate - Active Substances. Instruction and Application, Dosage

Name: Ethylmethylhydroxypyridine succinate

The Latin name of the substance Ethylmethylhydroxypyridine succinate

Aethylmethylhydroxypyridini succinas (genus Aethylmethylhydroxypyridini succinatis)

Chemical name: 2-Ethyl-6-methyl-3-hydroxypyridine succinate

Formula - C12H17NO5

Therapeutic substances Ethylmethylhydroxypyridine succinate- Antihypoxants and antioxidants

The nosological classification (ICD-10)

F10.3 abstinence
F40.0 Agoraphobia
F90.0 Violation of activity and attention
G24 Dystonia
G93.4 Encephalopathy, unspecified
I63 Cerebral infarction
I67.2 Cerebral atherosclerosis
I69 The effects of cerebrovascular disease
R41.3.0 * Reduced memory
R41.8.0 * Disorders intellectual mnesticheskie
T43.4 Poisoning neuroleptic-derivatives phenothiazine series, butyrophenone and thioxanthene

CAS code - 127464-43-1

Characteristics substance Ethylmethylhydroxypyridine succinate

White or slightly white with a white crystalline powder. Easily soluble in water.

Pharmacology
Mode of action - antioxidant, membrane, nootropic, cerebroprotective, adaptogenic, anxiolytic.

Inhibits lipid peroxidation, increase of antioxidant activity of the system, activates the energy-synthesizing mitochondrial function improves energy metabolism in the cell, it helps to maintain level macroergs, including under hypoxia stress. Activates intracellular protein and nucleic acid synthesis, enzymatic processes Krebs cycle promotes glucose utilization, synthesis and intra-cellular accumulation of ATP. Restores membrane structure and function, it has a modulating effect on the membrane-bound enzymes, ion channels, transport system neurotransmitter, receptor complexes, including Benzodiazepine-GABA, acetylcholine, improves synaptic transmission and interconnection structures of the brain.

Metabolism and improves blood flow to the brain, blood rheology and micro-circulation, immune system function, inhibits platelet aggregation. It has anti-hypoxic, cerebroprotective, anxiolytic, antistress, nootropic (improved memory, attention, mental performance), anti-hypnotic, about alcohol, anticonvulsant and antiparkinsonian Wegetotropona action. It lowers total cholesterol and LDL and causes the regression of atherosclerotic changes in the arteries (lipid-lowering and anti-atherogenic effect). It has anti-ischemic properties: improves blood flow, limiting the area of ischemic damage and stimulate repair processes. It increases the body's resistance to the effects of extreme factors and oxygen-dependent pathological conditions such as shock, stress, sleep deprivation, hypoxia, cerebrovascular accident, brain injury, ischemia, electric shock, physical and mental overload, conflicts, intoxication (ethanol, etc. ).. It slows down the aging process. Antialcoholic effect is the effect sober and motivation weakening and is used for the relief of withdrawal symptoms and the treatment of acute poisoning. Simultaneous treatment with alcohol intoxication is not exacerbated, and prevents it. Decreases resistance to psychotropic drugs and reinforces their action, which makes the ability to reduce therapeutic doses and the likelihood of adverse effects. Radioprotective properties can be used as a prophylactic measure radiation at high degree.

The experimental and clinical placebo-controlled studies have shown high efficiency oksimetiletilpiridina succinate in the treatment of ischemic stroke (100-1000 mg / day / drip), manifesting regression disorders of consciousness and symptoms of vasomotor instability, accelerating the recovery of motor function.

In children, the inclusion of the drug (10 mg / kg / day orally) in the scheme of therapy of non-paroxysmal supraventricular tachycardia and sick sinus syndrome, increased treatment efficiency on average by 20-27%.

Application of the substance Ethylmethylhydroxypyridine succinate

Injection: acute and chronic cerebral circulatory disorders, including ischemic stroke and its consequences; encephalopathy, dystonia; psychosomatic diseases; neurosis and neurotic disorders with anxiety manifestation of fear, emotional stress; disorders of memory and attention, disturbance of mental capacity; mental and neurological diseases in the elderly, cerebral atherosclerosis; relief of alcohol withdrawal syndrome, accompanied by neurosis and vegetative-vascular disorders; acute intoxication antipsychotics; acute purulent inflammation of the abdominal cavity: acute necrotizing pancreatitis, peritonitis (in the complex therapy).

Tablets: ischemic heart disease (complex therapy).

Contraindications

Hypersensitivity to the hydroxymethyl-ethylpyridine succinate and / or pyridoxine, acute human liver and kidneys, pregnancy, breast-feeding.

Restrictions of application of Ethylmethylhydroxypyridine succinate
Children under 18 years of age (safety and efficacy have not been determined).

Pregnancy and breast-feeding
Contraindicated (adequate clinical experience in pregnancy and during breast-feeding is not).

Side effects of Ethylmethylhydroxypyridine succinate substance
Nausea, dry mouth, allergic reactions.

Interaction

Enhances the effects of alcohol and CNS depressants (opioids, anesthetic, hypnotics, antipsychotics with sedating effect), muscle relaxants, and others. Antacids delay absorption (but do not reduce the extent of absorption) chlordiazepoxide. Chlordiazepoxide may weaken the effect of levodopa. Cimetidine, estrogen oral contraceptives, disulfiram and erythromycin chlordiazepoxide slow metabolism in the liver, increase in blood concentration and delayed excretion. Smoking can weaken the effect of chlordiazepoxide.

Overdose of Ethylmethylhydroxypyridine succinate

In case of overdose possible drowsiness.

Dosing and Administration of Ethylmethylhydroxypyridine succinate
Parenteral: in / m or / in (bolus or infusion).

In / jet (within 5-7 minutes) or a drip (40-60 drops per minute) is used as a solvent physiological sodium chloride solution. The dosage regimen is selected individually. The initial dose of 50-100 mg, 1-3 times a day, then gradually increase the dose to produce a therapeutic effect. The maximum dose - 800 mg / day.

Acute cerebrovascular disease: in the complex therapy - / drip 200-300 mg / day during the first 2-4 days, and then in / m to 100 mg 3 times a day. Duration of treatment - 10-14 days.

Encephalopathy (decompensation phase): in / bolus or infusion at 100 mg 2-3 times a day for 14 days, and then continue introduction / m to 100 mg / day for 14 days. Prevention vascular encephalopathy: a / m, 100 mg 2 times a day for 10-14 days.

Mild cognitive impairment in elderly patients, anxiety disorders: i / m, 100-300 mg / day for 14-30 days.

Abstinence syndrome: 100-200 mg / m 2-3 times a day or in / drop 1-2 times per day for 5-7 days.

Acute intoxication antipsychotics: a / c, 50-300 mg / day for 7-14 days.

Acute necrotizing pancreatitis, peritonitis: used in the pre- and postoperative period, the dosage regimen depends on the process prevalence, severity of the condition.

Inside: 0.1 g 3 times a day. Course Length - not less than two months. Repeated courses - on doctor's advice.

Precautions substance Ethylmethylhydroxypyridine succinate
Be wary of during the drivers of vehicles and people skills relate to the high concentration of attention.

Trading names of drugs with Ethylmethylhydroxypyridine succinate working substance

Trade Name Index 

2-ethyl-6-methyl-3-hydroxypyridine succinate, 3-hydroxy-6-methyl-2-ethylpyridine succinate, Astrox, Medomexi, Mexidant, Mexidol, Mexidol solution for injection 5%, Mexicor, Mexipridol, Mexiprim, Mexifin, Metostabil, Neurox, TCerekard, Emoxypine

Tetrazepam - Active Substances. Instruction and Application, Dosage

Name: Tetrazepam

The Latin name of the substance Tetrazepam

Tetrazepamum (genus Tetrazepami)

Chemical name: 7-Chloro-5- (1-cyclohexen-1-yl) -1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Formula - C16H17ClN2O

Therapeutic substances Tetrazepam - Drugs affecting neuromuscular transmission, anxiolytics

The nosological classification (ICD-10)

G24.3 Spasmodic torticollis
G54.1 Disorders of lumbosacral plexus
M15-M19 Arthrosis
M45 Ankylosing spondylitis
M54.3 Sciatica
M54.5 Pain in the lower back
M60 Myositis
M62.4 Contracture of muscle
M65 Synovitis and tenosynovitis
M77.0 Medial epicondylitis
M77.1 Lateral epicondylitis
R25.2 Cramp and spasm

CAS code - 10379-14-3

Pharmacology

Mode of action - muscle relaxant, central.

Stimulates the benzodiazepine receptors, it increases the GABA-receptor sensitivity to the mediator and enhances the inhibitory effect of GABA in the CNS. Decreases anxiety subcortical brain structures (anticonvulsant activity), inhibits polisinapticheskie spinal reflexes. It reduces emotional stress, reduces anxiety, fear, anxiety (anxiolytic and sedative effect).

It passes through tissue barriers, including GEB. T1 / 2 - 14-16 h.

Application of the substance Tetrazepam

Muscle contractures, neurological contracture with spasms, torticollis, myositis, accompanied by severe pain, back pain and lower back, pain in tendon diseases (epicondylitis, tendonitis) and joints for kinesis-hydrotherapy.

Pregnancy and breast-feeding

Contraindicated during pregnancy (especially in I trimester). At the time of treatment should stop breastfeeding.

Side effects of Tetrazepam substance 

Drowsiness, dizziness, euphoria, paradoxical reactions (irritability, aggressiveness), muscle weakness, ataxia, skin rash, itching; when abrupt cancellation: irritability, anxiety, myalgia, tremor, insomnia, nightmares, nausea, vomiting, convulsions, decreased reaction rate, a feeling of fatigue.

Interaction

(Mutually) effects of muscle relaxants, antipsychotics, tranquilizers, tricyclic antidepressants, alcohol, sedatives and hypnotics.

Dosing and Administration of Tetrazepam

Inside, in a hospital in an initial dose of 50 mg at night; gradually increase the dose of 25-50 mg, distributing it into several times, until the effective therapeutic dose of 150 mg in 3 divided doses; if necessary - 300-400 mg / day. When outpatient treatment starting dose is 25 mg in the evening, gradually increase the dose to 25 mg, distributing it into several stages; effective dose - 75-100 mg / day. Babies - 4 mg / kg / day in divided doses. Elderly patients - half the dose. Cancel the drug should be gradual. Kinesis hydrotherapy - 50 mg for 1 hour before the session.

Special instructions for Tetrazepam

Should not be used during the drivers of vehicles and people skills relate to the high concentration of attention. At the time of treatment should refrain from drinking alcohol.

Trading names of drugs with Tetrazepam working substance

Trade Name Index

Myolastan

Chlordiazepoxide - Active Substances. Instruction and Application, Dosage

Name: Chlordiazepoxide

The Latin name of the substance Chlordiazepoxide

Chlordiazepoxydum (genus Chlordiazepoxydi)

Chemical name: 7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amino-4-oxide (as hydrochloride)

Formula - C16H14ClN3O

Therapeutic substances Chlordiazepoxide - anxiolytics

The nosological classification (ICD-10)

F07 Personality disorders and behavior caused by disease, injury, or dysfunction of the brain
F10.3 abstinence
F10.4 abstinent state with delirium
F10.5Alcoholic psychosis
F11 Mental and behavioral disorders due to use of opioids
F20 Schizophrenia
F32 Depressive episode
F40.0 Agoraphobia
F41.1 Generalized anxiety disorder
F42 Obsessive-compulsive disorder
F44 Dissociative [conversion] disorders
F45 Somatoform disorders
F51.0 Insomnia inorganic etiology
G44.2 tension headache types
G47.0 Disorders of falling asleep and maintaining sleep [insomnia]
G56.4 causalgia
L29 Itching
N50.8.0 * Menopause in men
N94.3 syndrome premenstrual tension
N95.1 menopausal and menopausal status of women
R06.6 Hiccups
R07.2 Pain in the heart
R25.2 Cramp and spasm
R25.8.0 * hyperkinesia
R45.1 Restlessness and agitation
R45.4 Irritability and anger
Z100 * CLASS XXII Surgical practice
Z54.0 recovery period after surgery

CAS code - 58-25-3

Characteristics substance Chlordiazepoxide
Anxiolytic, benzodiazepine derivative.

White or light yellow crystalline powder. Practically insoluble in water, it is soluble in alcohol; as the hydrochloride - is soluble in water.

PharmacologyMode of action - anxiolytic, sedative, hypnotic, muscle relaxant, central.

Interacts with specific benzodiazepine receptors located in postsynaptic GABAA receptor complex in the cerebral cortex, amygdala, hippocampus, hypothalamus, cerebellum, striatum, and spinal cord. Increases the sensitivity of neuronal GABA receptors to GABA enhances GABA neurotransmission, blocks polysinaptic reflexes.

After oral administration, it is well absorbed from the gastrointestinal tract (food slows absorption); Cmax when administered single dose reached after 0.5-4 hours and the equilibrium concentration in the blood is 5-12 days after the beginning of reception. Plasma protein binding is 96%. T1 / 2 chlordiazepoxide from plasma is 7-28 hours, the Cmax of the main metabolite (desmethyl-chlordiazepoxide.) - 8-24 hours The liver is intensive metabolism (N-demethylation, deamination, hydroxylation) to form active derivatives (desmethyl-chlordiazepoxide, demoksepam , desmethyl-diazepam, oxazepam). It passes through GEB, placenta, enters the breast milk; slowly absorbed from the muscle tissue. After the treatment, the metabolites found in the plasma for a few days or even weeks. T1 / 2 - 5-30 hours (chlordiazepoxide), 18 hours (desmethyl-chlordiazepoxide), 14-95 hours (demoksepam), 30-100 hours (dezmetildiazepam), 5-15 hours (oxazepam). Report mostly kidneys (1-2% unchanged). Accumulation of chlordiazepoxide and its active metabolites with repeated use significantly.

Older people chlordiazepoxide absorption and metabolism are slower, significantly slowing down the metabolic transformation at the defeat of the liver.

It has a marked sedative effect on the central nervous system. It suppresses the alarm, excitement, emotional stress. Weakens the obsessions and fears, increases susceptibility to hypnosuggestive therapy. Has anti-panic effect, it relieves tremors, has a weak anticonvulsant effect. It reduces the severity of anxiety and fear associated with the upcoming surgery.

In large doses, can reduce agitation. Exhibits mild hypnotic effect which is expressed usually in the first 3-5 days of treatment, further positive effects on sleep due to the elimination of various psychogenic stimuli. It causes moderate muscle relaxation.

Relieves the symptoms of acute alcohol withdrawal symptoms such as agitation, nervousness, anxiety, anxiety, tremors, and others. Increases appetite, it has a weak analgesic effect.

Reproduction studies in animals showed that the introduction of chlordiazepoxide in rats at doses of 10, 20 and 80 mg / kg / day did not cause of congenital malformations and disorders of neonatal growth, as well as violation of lactation in females. In another study, when administered dose of 100 mg / kg / day a significant reduction in the fertilization rate was revealed marked reduction of body weight and survival in neonatal rats.

Application of the substance Chlordiazepoxide

Neurotic state accompanied by anxiety, agitation, increased irritability, emotional stress, insomnia; neurotic ataxia, tension headache, false angina, esophageal spasm, causalgia, facial gemispazm, hysterical state (hysterics, amblyopia, mutism, paralysis), psychogenic stupor, hiccups; nevrozo- and psychopathic disorders in patients with cerebral atherosclerosis, organic brain damage; infectious delirium, withdrawal syndrome in patients with alcoholism and drug addiction; increased skeletal muscle tone, hyperkinesia rheumatic and neurotic; menopause, premenstrual syndrome, vascular dystonia; premedication (preparation of patients for operations and lengthy diagnostic procedures), the postoperative period; complex therapy in schizophrenia with symptoms of neurosis, as well as in diseases accompanied by itching, irritability, insomnia, including eczema.

Contraindications
Hypersensitivity, severe myasthenia gravis, respiratory depression, angle-closure glaucoma, acute liver disease and / or kidney disease, pregnancy (I term), breast-feeding, age up to 4 years.

Restrictions of application of Chlordiazepoxide
Glaucoma, liver and / or kidney problems, sleep apnea syndrome, severe heart and respiratory failure, ataxia (except neurotic), psychosis (possible paradoxical increase in symptoms), drug or alcohol dependence (except for the treatment of acute withdrawal syndrome), pregnancy ( II and III trimester), advanced age.

Pregnancy and breast-feeding

It contraindicated in I trimester of pregnancy (increases the risk of congenital malformations when administered during this period). In II and III trimester of pregnancy is possible if the expected effect of therapy outweighs the potential risk to the fetus. At the time of treatment should stop breastfeeding.

Side effects of Chlordiazepoxide substance 

From the nervous system and sensory organs: drowsiness, fatigue, impaired memory and concentration, mental retardation and motor reactions, muscle weakness, gait disturbance, ataxia, confusion, disorientation, dizziness, headache, EEG changes.

Cardio-vascular system and blood (blood, hemostasis): tachycardia, palpitations, hypotension (at high doses), thrombocytopenia, agranulocytosis.

From the digestive tract: dry mouth, nausea, constipation or diarrhea, intestinal colic, abnormal liver function, jaundice of the skin.

Allergic reactions: skin rash, itching, peeling skin.

Other: difficulty breathing, urinary retention, menstrual disorders, libido change (increase or decrease).

Possible addiction, drug dependence, withdrawal syndrome and others.

Interaction

Enhances the effects of alcohol and CNS depressants (opioids, anesthetic, hypnotics, antipsychotics with sedating effect), muscle relaxants, and others. Antacids delay absorption (but do not reduce the extent of absorption) chlordiazepoxide. Chlordiazepoxide may weaken the effect of levodopa. Cimetidine, estrogen oral contraceptives, disulfiram and erythromycin chlordiazepoxide slow metabolism in the liver, increase in blood concentration and delayed excretion. Smoking can weaken the effect of chlordiazepoxide.

Overdose of Chlordiazepoxide

Symptoms: oppression CNS varying degrees of symptoms (from somnolence to coma) - marked drowsiness, lethargy, weakness, loss of muscle tone, long-term mental confusion, disorientation, slurred speech, depression of reflexes, coma; also possible respiratory depression, hypotension.

Treatment: induction vomiting, immediate gastric lavage, monitoring of vital functions, symptomatic therapy, in / in infusion solutions (to increase urine output), the provision of adequate ventilation; in the case of hypotension - introduction of norepinephrine. When driving the development should not be used barbiturates. As a specific antidote used BZ antagonist flumazenil receptors (in the hospital). Hemodialysis is ineffective.

Dosing and Administration of Chlordiazepoxide

Inside. Doses (single and daily) and duration of treatment are selected strictly individually, depending on the nature and course of the disease, tolerance and others. Treatment should be started with the lowest effective dose corresponding to a particular form of pathology.

The usual single dose for adults - 5-10 mg, the usual daily - 20-60 mg (2-4 doses). When the state of stress in combination with sleep disorders - 10-20 mg 1 time per day for 1-2 hours before bedtime. In psychiatry - 50-100 mg / day, with alcohol withdrawal syndrome - 300 mg / day in 3-4 divided doses.

Patients are elderly, debilitated patients, patients with diseases of the liver and / or kidney disease should be prescribed lower doses (single - 2.5-5 mg). The treatment duration should not exceed 2.5 months. A second course (if necessary) - no earlier than 3 weeks.

Children starting at age 4 years dose (and duration of treatment) are selected individually depending on the age, body weight and others.

Precautions substance Chlordiazepoxide

Note that the combination of anxiety with depression may attempt suicide.

To apply caution in conjunction with other psychotropic drugs. Should not be administered concurrently with MAO inhibitors and phenothiazines.

With prolonged use (over several months), particularly at high doses, may addiction, drug dependence. Abolition of chlordiazepoxide should be done gradually by reducing the dose to reduce the risk of withdrawal syndrome characterized by tremor, cramps, abdominal and muscle cramps, vomiting, sweating. In abrupt cancellation also possible agitation, anxiety, autonomic disorders, insomnia.

Do not take chlordiazepoxide more than 4 weeks without re-evaluation of the patient to decide whether to continue therapy.

The probability of side effects is higher in the elderly.

Prolonged use should be periodically monitored picture peripheral blood and liver function.

There are reports that in the treatment of chlordiazepoxide mental patients and children with the aggressive behavior traits observed paradoxical reactions (psychomotor agitation, rage, etc.).. In the case of paradoxical reactions, treatment should be discontinued immediately.

It should be borne in mind that chlordiazepoxide can reduce mental alertness in children.

It must be borne in mind that there are reports of effects on blood coagulation in patients taking oral anticoagulants simultaneously and chlordiazepoxide (in a clinical study of the causes and consequences of this interaction has not been established). There are some reports of exacerbation of porphyria under the action of chlordiazepoxide. Hypoproteinemia may predispose to increase the frequency of sedative side effects.

During treatment and for 3 days after its cancellation should be deleted reception alcohol; drivers of vehicles and people whose work requires quick mental and physical reactions, and is also associated with high concentration of attention, should not engage in professional activities during this period.

Special instructions for Chlordiazepoxide

Keep in mind that anxiety or tension associated with everyday stress usually does not require treatment with an anxiolytic.

Trading names of drugs with Chlordiazepoxide working substance

Trade Name Index

Napoton, Radepur 10, Hlozepida coated tablets, 0.005 g, Elenium