Pharmacological properties

Pharmacodynamics. medicament contains a combination of neurotropic active agents of a complex of vitamins B. vitamins which are a part: thiamine (v1), a pyridoxine (v6) and cyanocobalamine (v12) play a special role as coenzymes in intermediate metabolism in central nervous system and peripheral nervous system.

As well as all other vitamins, they are irreplaceable nutrients which cannot directly be synthesized in an organism.

Therapeutic introduction to an organism of _{1 vitamins B} , In ₆ and In ₁₂ fills insufficient intake of vitamins C with food that provides existence in an organism of necessary amount of coenzymes. Therapeutic use of these vitamins in various diseases of nervous system is directed to, on the one hand, to compensate at the same time existing insufficiency (perhaps because of increase in the requirement of an organism caused directly by a disease) and with another — to stimulate natural mechanisms of restoration. In researches on animals the analgeziruyushchy action of a complex of vitamins B is proved.

_{1 Vitamins B} , In ₆ and In ₁₂ have very much hypotoxicity and have no potential risk for the person. There are no data on cancerogenic, mutagen or teratogenic properties of these vitamins for today.

Pharmacokinetics

Thiamine. The t _½ makes about 4 h. In a human body about 30 mg of thiamine can remain. Taking into account fast metabolism the reserve stocks are very limited, they are spent in 4–10 days.

Piridoksin. In a human body about 40-150 mg can remain, 1.7-3.6 mg are removed with urine per day.

Cyanocobalamine. _{12 vitamin B} remains generally in a liver. Speed of metabolism is 2.5 mkg/days or 0.05% of quantity which remains. _{12 vitamin B} is generally removed with bile and reabsorbirutsya substantially at enterohepatic circulation.

Indication

Treatment of neuritis and neuralgia, such, as:

• epileptiform neuralgia;
• intercostal neuralgia;
• sciatica;
• lumbar syndrome (lumbago);
• plexitis (cervical and brachial plexus);
• radicular neuritis owing to degenerative diseases of a backbone;
• prozoplegiya (damage of a facial nerve).

Use

In oil introduction.

In hard (sharp) cases: 1 ampoule a day before elimination of acute symptoms.

After reduction of expressiveness of symptoms or in cases of moderate weight: 1 ampoule 1–3 times a week. For strengthening of effect or continuation of a therapeutic course after injections or for prevention of a recurrence the tablet medicament Neurobion, coated is recommended.

Contraindication

Hypersensitivity to medicament components. it is contraindicated to p to apply

_{1 Vitamin B} in allergic diseases. it is contraindicated to p to apply

_{6 Vitamin B} in a peptic ulcer of a stomach and duodenum in an aggravation stage (as increase in acidity of gastric juice is possible). _{12 Vitamin B} it is contraindicated to p to apply

in an erythremia, a hyperglobulia, a thrombembolia.

Side effects

Side effects on the frequency of emergence classify

by such categories: very often (≥1/10), it is frequent (≥1/100, 1/10), infrequently (≥1/1000, 1/100), is rare (≥1/10,000, 1/1000), is very rare (1/10,000), it is unknown (frequency is not determined by the available data).

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from nervous system

Does not know to

— prolonged use (more than 6-12 months) in doses of 50 mg of _{6 vitamin B} can daily lead to peripheral touch neuropathy, nervous excitement, an indisposition, dizziness, a headache.

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from a GIT

Does not know to

— gastrointestinal disorders, including nausea, vomiting, diarrhea, an abdominal pain, increase in acidity of gastric juice.

from the immune system

It is very rare — reactions of hypersensitivity, the increased sweating, tachycardia, an acute anaphylaxis, an anaphylaxis, skin reactions, including an itching, urticaria.

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General disorders

Does not know to

— reactions in the injection site.

Special instructions

should not temporarily administer the Drug in / century

Parenteral administration of _{12 vitamin B} can influence diagnosis of a funicular myelosis or pernicious anemia.

during long intake of _{6 vitamin B} (more than 6-12 months) in doses of 50 mg daily or 1000 mg/days (more than 2 months) can lead

to reversible peripheral touch neuropathy. In case of symptoms of peripheral touch neuropathy (paresthesia) it is necessary to modify a dose of medicament and if it is necessary, to stop treatment.

Drug contains compounds of sodium. Patients who are on a saltless diet need to consider it. Each ampoule may contain residues of potassium.

As Neurobion contains _{6 vitamin B} , it is necessary to use with care medicament to patients with a round ulcer of a stomach and duodenum in the anamnesis, with the profound renal failures and a liver.

to Patients with new growths, except for the cases which are followed by megaloblastny anemia and deficiency of _{12 vitamin B} , should not use drug.

Drug is not used in severe or acute form of a decompensation of warm activity and stenocardia.

Use during pregnancy and feeding a breast

Drug is appointed only after careful assessment of a ratio of advantage and risk as there are not enough data on safety of use of medicament during pregnancy.

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_{1 Vitamins B} , In ₆ and In ₁₂ are excreted in breast milk. High concentrations of _{6 vitamin B} can oppress products of milk. Researches on extent of secretion of vitamins B breast milk were not conducted. The decision on the feeding termination by a breast or uses of medicament should be accepted taking into account need of administration of medicament for mother. In case of need uses of medicament it is necessary to stop feeding by a breast for this period.

Children. There are no sufficient data concerning use of medicament for children.

Ability to influence speed of response at control of vehicles or other mechanisms. Drug does not affect ability to run vehicles and to work with mechanisms. In cases if during medicament treatment note dizziness, it is necessary to refrain from control of vehicles and work with mechanisms.

Effect of thiamine is inactivated by

Interaction

5-fluorouratsily as the last competitively inhibits phosphorylation of thiamine in thiamine pyrophosphate. loopback diuretics, for example furosemide which brake a canalicular reabsorption at long therapy can cause increase in excretion of thiamine and, thus, reduce thiamine level.

Contraindicated simultaneous use with a levodopa as _{6 vitamin B} can reduce expressiveness of protivoparkinsonichesky action of a levodopa. The concomitant use with antagonists of a pyridoxine (for example an isoniazid, gidralazin, Penicillaminum or Cycloserinum), oral contraceptives can increase the need for _{6 vitamin B} .

Consumption of the drinks containing sulfites (for example wine), increases thiamine degradation.

Overdose

Vitamin v1 has wide therapeutic range. very high doses (10 g) show kurarepodobny effect, reducing conductivity of nervous impulses.

_{6 Vitamin B} has very much hypotoxicity.

Excessive use of _{6 vitamin B} in doses of 1 g/days within several months can result

in neurotoxic effects.

Neuropathy with an ataxy and disorders of sensitivity, cerebral spasms with changes on the electroencephalogram and also in some cases hypochromia anemia and seborrheal dermatitis were described after introduction in a dose of 2 g/days

_{12 Vitamin B} : after parenteral administration (in rare instances — after oral administration) medicament in higher doses, than recommended, noted allergic reactions, eczematic skin disturbances and a benign form of an acne. At prolonged use in high doses the disturbance of activity of enzymes of a liver, pain in heart, hypercoagulation are possible.

Storage conditions

B the place protected from light at a temperature not above 2-8 °C.

Relevant information

from the moment of discovery of the majority of vitamins B the beginning hkh the relation to them of scientists and the practicing doctors constantly changes century. they are an effective remedy of correction of various metabolic disorders, recede into the background after discovery of the next new active ingredient. however for today such medicaments as neurobion, are relevant in practice of the doctor. importance of vitamins for a normal course of various processes in a human body is proved long ago, and at the same time more difficult processes in which a key link are vitamins are constantly studied, in particular groups of century with understanding of subtleties of physiological and pathological processes also the relevance of use of these of the studied active ingredients comes long ago.

As shows therapeutic effect of Neurobion

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Neurobion represents itself a combination from 3 vitamins of group B — disulfide thiamine (in an injection form of thiamine a hydrochloride) (To ₁ ), a hydrochloride pyridoxine (To ₆ ) and cyanocobalamine (To ₁₂ ). All of them are considered as neurotropic vitamins and at the same time are irreplaceable, that is are not synthesized in a human body and have to arrive from the outside.

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Thiamine — _{1 vitamin B} , to it assigns a key part in processes of exchange of amino acids, fats (in particular sphingolipids) and carbohydrates. It is considered the major antinevritichesky factor (A.K. Yarosh, 2009). Thiamine is a water-soluble substance therefore it is not deposited in tissues of a human body and regular receipt it with food is necessary. After absorption in blood thiamine is exposed to phosphorylation and transformation to an active form — thiamine pyrophosphate. Thiamine the disulfide synthesized in the 60th years the 20th century (G.V. Ramenskaya) became the original pharmacological decision: it represents a lipophilic form of _{1 vitamin B} which is characterized by bigger bioavailability. In particular, lipophilic forms of thiamine get through GEB, show antidepressive (thanks to inhibition of receptors of benzodiazepine) and neurotyre-tread (stimulates emission of acetylcholine) the effect, slows down the return serotonin reuptake (that is relevant for treatment of alcoholism) (O.A. Gromova, 2017). Besides, thiamine the disulfide has antioxidant properties — it inhibits processes of peroxide oxidation of lipids in mitochondrions of a liver and free radical oxidation of oleic acid (Lukienko P.I., 2000).

Heavy deficiency of _{1 vitamin B} is associated with development of two diseases: beriberi and its special case — Korsakov's syndrome — Wernicke. Beriberi is a disease which develops owing to insufficient intake of thiamine from the outside (food the refined products, the insufficient use of flour products and bean) or the excess use of the products containing a thiaminase (fresh fish or seafood). Also intensive consumption of such drinks as tea and coffee, associate with oppression of processes of absorption of thiamine a mucous membrane of a GIT. Refer the general weakness, muscular dystrophy, encephalopathy, a peculiar polyneuropathy and also sluggish paresis or plegiya to manifestations of beriberi.

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Korsakov's Syndrome — Wernicke is regarded as a special case of beriberi. The reason is that alcohol directly interferes with thiamine phosphorylation processes, reducing quantity of its active metabolite. Dysmnesias (fixating and a retrogradna amnesia), a disorientation in the place and time and also emergence of false memoirs are as a result observed (confabulation) and change in memory of time of events which happened in reality (pseudoreminiscence) (V.G. Ashirova, 2018).

Piridoksin's

hydrochloride is an inactive form of _{6 vitamin B} . After absorption in blood it is exposed to phosphorylation therefore the active form — piridoksal-5-phosphate is formed (Oka T., 1999). Its biological role is that it is a component of many enzymes which are responsible for synthetic reactions, transaminations, decarboxylations and also desulphonations and racemizations aminoxylot. Besides, piridoksal-5-phosphate acts as a key coenzyme of phosphorylase of a glycogen. The fact that it regulates processes of digestion of glucose neurons is considered important neurologic effect of a pyridoxine. Besides, it is an integral part of processes of exchange of proteins and fats, formation of sphingolipids, a gem in erythrocytes.

Piridoksal-5-fosfat acts as

as a coenzyme of the decarboxylases which are responsible for synthesis of biogenous amines. Therefore the deficiency of _{6 vitamin B} is associated with disturbance of synthesis of all key neurotransmitters: GAMK, dopamine, serotonin, histamine.

Tsianokobalamin also famous as _{12 vitamin B} or an external factor of Kastl — substance which is not synthesized in a human body but only it is soaked up with food. The internal factor of Kastl — specific protein which is produced by covering cells of a stomach is responsible for its absorption. This process in atrophic gastritis, considerable disturbances of structure of intestinal microflora is broken and also at monotonous food by mainly refined products. Traditionally cyanocobalamine is considered antianemic vitamin, however in case of its deficit not only the synthesis of a gem is broken, but also there comes the demyelination of nerve fibrils leading to their death. As a result various neurologic disorders develop. Today modern writers associate with deficiency of _{12 vitamin B} even such heavy neurologic disorders as Parkinson's disease (N.A. Savelyeva-Kulik, 2019) and senile dementia (A. Antonyuk, 2016).

Should note

that contained in the list Neurobion components cause not only cooperative therapeutic effect, an important role is played by synergism of thiamine, a pyridoxine and cyanocobalamine in their influence on metabolic processes in the haematogenic cells and cells of nervous system (O.A. Gromova, 2016).

Combination of vitamins of group B not only considerably influences exchange processes in neurons, but also causes the significant analgezivny effect (instruction of MZ of Ukraine).

Route of administration and selection of a dose of Neurobion

Neurobion is issued in two dosage forms — tablets and solution for injections. In both cases it is recommended to take medicament 1 r / days. At the same time the disulfide/hydrochloride thiamine dose in both dosage forms makes 100 mg, a hydrochloride pyridoxine — in an injection form is twice less, than in tableted (100 mg against 200 mg), and cyanocobalamine — in an injection form exceeds that in the tableted form more than by 4 times (1 mg against 240 mkg). Such difference in doses of different forms of introduction can be explained with various bioavailability of active components at different ways of introduction. Though was considered earlier that it is impossible to mix _{1 vitamins B} , In ₆ and In ₁₂ , however the modern pharmacological decision assumes a combination of one lipophilic and two hydrophilic molecules in alkalescent solution carrier that provides the maximum bioavailability of each component and interferes with formation of insoluble complexes.

Solution is usually applied by

to injections in the conditions of a hospital or a day hospital — the medicament is administered by medical personnel in oil. After elimination of acute manifestations of pathological process it is recommended to transfer the patient to the tableted form — the patient can independently take a pill.

At acute condition Neurobion is accepted in such mode: 1 injection (1 ampoule of medicament — 3 ml) in day or up to 3 tablets/days. After improvement of the general state the dose can be lowered to 1 tablets/days, and injections in oil — to carry out 1 r / days with an interval of 1-2 days (instruction of MZ of Ukraine). In case of improvement or stabilization of a condition of an injection it is possible to do not every day, and with an interval.

General principles of appointment Neurobion assume that in process of improvement of the general state the patient is transferred from an injection form on tableted. The maximum duration of the general course of therapy at the same time is no more than 4 weeks

Indications of Neurobion

Neurobion is the medicament which is widely applied in neurologic practice. Treated pathological processes at which Neurobion is included in structure of the complex therapeutic scheme:

• neuralgia of cranial nerves, in particular trifacial and also prozopalgiya (damage of a facial nerve);

• a radicular syndrome — a complex of the sensitive and motive disorders caused by infringement of roots of chest and lumbar segments of a spinal cord (in particular, intercostal neuralgia, a lumbago, a sciatica, etc.);

• injuries of neuroplexes (for example humeral, cervical, etc.).

Other possible perspective directions of clinical use Neurobiona

Drug represents a combination of 3 active components therefore, except the main indications, it can be applied in such clinical situations:

• polyneuropathy diabetic (A.K. Yarosh, 2009) and toxic genesis;

• alimentary (connected with diets or external circumstances) a heavy vitamin deficiency of group B;

• beriberi;

• alcoholic psychosis, alcoholic polyneuropathy (Korsakov's syndrome);

• in ophthalmologic practice — treatment of neuropathy of an optic nerve (A.E. Egorov, 2013);

• thanks to existence in structure of a pyridoxine Neurobion can be appointed in complex therapy of a carpal tunnel syndrome (Jacobson M.D., 1996);

• piridoksinsoderzhashchy medicaments are also relevant as supportive application for treatment of toxic neuropathy (after receiving a rate of antitubercular drugs) (L.M. Voron_na, 2000);

• medicament can be used in dermatological practice — for treatment of various dermatitis (G.P. Tikhonov, 2014), in particular seborrheal dermatitis (Stone O.J., 1989);

• can be the interesting indication to use Neurobion symptomatic treatment of a premenstrual syndrome. The pyridoxine proved as the nonspecific medicine reducing the number of complaints and degree of unpleasant feelings (Brush M.G., 1988);

• as the pyridoxine is characterized by anti-lactogenic effect (Gupta T., 1990), appointment Neurobion to women who stop feeding by a breast, for the fastest oppression of a lactation is possible. However in literature there are no unambiguous data on as far as vitamins of group B cosecrete in breast milk and as influence the child. Therefore from the moment of prescribing of medicament the child has to be completely transferred to independent food (or artificial feeding);

• as the combination of vitamins of group B is characterized by the significant analgesic effect, Neurobion can be recommended as a part of complex therapy of any chronic pain syndrome as at this type of pain always note a neuropatichesky component.

it is important to p to know

Feature of use of Neurobion

about risks which can be caused by medicament overdose. In particular, one-stage hit in blood of a high dose of _{1 vitamin B} can cause anaphylactic reaction. It is connected with the fact that thiamine is capable to induce nonspecific degranulation of mastocytes.

Drug is contraindicated to

in the hematologic diseases connected with increase in quantity of erythrocytes and level of hemoglobin in blood (for example an erythremia) and also in the presence of thromboembolic states in the anamnesis. The property of _{12 vitamin B is the reason of it} to increase absorption of iron and blood clotting.

is not recommended to take the Drug constantly as the overdose of a pyridoxine can lead to development of peripheral neuropathy in touch type (instruction of MZ of Ukraine). Besides, high doses of _{6 vitamin B} lead to a photosensitization (Morimoto K., 1996).

Conclusion

Neurobion is the modern combined medicament which components are necessary for normal functioning of nervous system and other systems of an organism. Drug is produced in two forms that allows to apply conveniently it as in the conditions of a hospital at various weight of a condition of the patient, and is out-patient. At the same time active ingredients and auxiliary components are picked up so that to provide the maximum bioavailability and the maximum therapeutic effect. Neurobion is not exclusively neurologic drug, it is also suitable for use in dermatology, gynecology, gerontology, etc.