NEUROBION 10 000 HYPACK 5 INJECTIONS

THERAPEUTIC INDICATIONS: Deficiency of the components of the formula.Neurobion is indicated as part of the treatment of various painful conditions such as back pain, muscle pain, sciatica, radiculitis, alcoholic polyneuropathy, diabetic neuropathy, torticollis, peripheral neuralgia, facial neuralgia, trigeminal neuralgia, intercostal neuralgia, postherpetic neuralgia.

Pharmacokinetics IN HUMANS: Vitamins B1, B6 and B12 are involved in the metabolism of all body cells and show activity particularly important in hematopoiesis and the functioning of nervous system cells, for which they have been called vitamins neurotropic.

Thiamine (vitamin B1): Thiamin is absorbed in the small intestine through two mechanisms: a) by active transport and, b) by passive diffusion. There appears to be an energy-dependent specific transporter and sodium. The active absorption of thiamine is greater in the jejunum and ileum. The intestinal transport of thiamine radiolabeled human has a Vmax of 31.5 mmol (8.3 mg) and Km of 45.6 mmol (12.0 mg).

Thiamine is transported by the blood of the portal vein to the liver. 20 to 30% of thiamine present in the plasma of normal adults is protein bound in the form of thiamine pyrophosphate. The average total amount in the normal adult is approximately 30 mg in high concentrations in heart, liver, kidneys, brain and skeletal muscle. Approximately 50% of the total body thiamine is present in the muscles. The biological half-life of radiolabeled thiamine is 9 to 18 days. Since Thiamine is not stored in large amounts in tissues, it is necessary a continuous supply of the vitamin.

About 80% of the total body thiamine is thiamine pyrophosphate, 10% is thiamine triphosphate and the rest is as thiamine monophosphate. We found 25 to 30 urinary metabolites of thiamine in humans of which override the pyrimidine-carboxylic acid, acid and acid tiaminacético thiazoleacetic acid.

Thiamine and its metabolites are primarily excreted in the urine and a small amount is excreted in the bile. When administered orally or parenterally, this vitamin is rapidly converted to thiamine pyrophosphate and thiamine triphosphate in the tissues. Thiamine tissue that exceeds the needs and storage capacity is rapidly excreted in the urine in free form. Tissue degradation performed totaling approximately one milligram of thiamine daily amount corresponding to the daily.When intake is less than that amount, the thiamine is not in the urine or does it in very small quantities.

Thiamine pyrophosphate functions as a coenzyme in the decarboxylation and transcetolación a-keto acids. In a more functional, thiamin participates in various neurophysiological processes.

Thiamin is involved in various processes of neurotransmission. In preclinical studies have shown that in thiamine deficiency, the turnover of acetylcholine and its use are decreased in the cerebral cortex, midbrain, diencephalon and brain stem, the synthesis of catecholamines in the brain decreases, including significant reductionsthe contents of noradrenaline from the cerebral cortex, the hippocampus and olfactory bulb; serotonin uptake by synaptosomes cerebellar decreases, 5-hydroxyindoleacetic acid (catabolite of serotonin), is significantly increased without altering the levels of tryptophan and are reduced concentrations of glutamate, aspartate, gamma-aminobutyrate and glutamine.

Regardless of your role as a coenzyme have been observed other important actions of thiamine. Thiamine antagonists affect impulse conduction in peripheral nerves after stimulation of thiamine is released from the membrane preparations of brain, spinal cord and sciatic nerves, phosphorylated derivatives of thiamine are related proteins sodium channel. Thiamine may play a fundamental role in controlling the conductance of sodium in axonal membranes, as well as in other processes neurofunctional.

Pyridoxine (vitamin B6): The absorption process of the three primary forms of vitamin B6 is carried out mainly by a process of passive non-saturable transport, mainly in the jejunum. After hydrolysis of the phosphorylated forms and their uptake by the intestine, each is phosphorylated and then retained. However, the forms of vitamin B6 which are released from the basolateral side of the membrane of the intestine are mainly unphosphorylated forms.

In general, human studies show an inverse correlation between the amount of glucoside of pyridoxine from the diet and bioavailability. About 58% of pyridoxine glucoside is bioavailable. Digestion of food and the presence of fiber in the diet may limit the bioavailability of vitamin B6. Vitamin B6 is transported in the blood, plasma and erythrocytes.

Pyridoxal and to a lesser extent pyridoxal phosphate are bound to albumin and hemoglobin.

The liver is the organ responsible for most of the metabolism of vitamin B6. As a result, this body provides the active form of vitamin B6 (pyridoxal phosphate) for circulation and other tissues. The three forms are not phosphorylated converted to their respective phosphorylated forms of the pyridoxine-kinase, which uses as cofactors zinc and ATP. Pyridoxamine phosphate and pyridoxine phosphate can be converted to pyridoxal phosphate by a flavin mononucleotide oxidase. Pyridoxal coming from the dephosphorylation and the derivative of nutritional sources or drug, may be converted to 4-pyridoxic acid in a non-reversible reaction which participates flavin dinucleotide and an adenylate aldehyde oxidase. This reaction occurs in the human liver, but whether the case in other tissues.

Pyridoxal phosphate and pyridoxal comprise about 75 to 80% of the total circulating vitamin B6 in the plasma, after these forms, pyridoxine is the most common form, which is picked up by the tissues to be converted to phosphate pyridoxine, however, lack sufficient many tissues oxidase activity to convert pyridoxine phosphate pyridoxal phosphate.

The various functions of vitamin B6 in humans are complex and intertwined. Due to the reactivity of pyridoxal phosphate with amino acids and several nitrogen compounds, the biochemical functions of vitamin B6 are concentrated around these molecules. In these functions, the pyridoxal phosphate acts as a catalyst for many reactions.

Pyridoxal phosphate is involved in gluconeogenesis through its participation in transamination reactions and the action of glycogen phosphorylase. The activities of glycogen phosphorylase in the liver and muscle are decreased in rats with vitamin B6 deficiency but a vitamin deficiency alone does not produce mobilization of vitamin B6 stored in the muscle. In experimental animals were observed increased concentrations of linoleic acid and linolenic acid and d-low concentrations of arachidonic acid in liver phospholipids. This effect is accompanied by alterations in the metabolism of amino acids (homocysteine) and changes in the phospholipids and fatty acids associated with them.

The correlation between vitamin B6 and cholesterol also remains unclear. In humans, a deficiency of vitamin B6 is not accompanied by significant changes in serum cholesterol.

In the erythrocyte pyridoxal phosphate functions as a coenzyme of transaminases.Both pyridoxal phosphate as pyridoxal bind to hemoglobin. Pyridoxal phosphate attached to the alpha chain of hemoglobin, increases the affinity of the molecule by oxygen, while pyridoxal phosphate weakly bonded to the beta chain decreases the binding affinity for oxygen. Severe and chronic deficiency of vitamin B6 can cause microcytic hypochromic anemia.

Some patients with sideroblastic anemia and other forms of anemia respond well to therapy with pyridoxine.

Pyridoxal phosphate is a coenzyme involved in enzymatic reactions leading to the synthesis of several neurotransmitters, such is the case of serotonin (from tryptophan), taurine, dopamine, norepinephrine, histamine and alpha-aminobutyric acid. Neurological disorders have been reported in infants and animals deficient in vitamin B6. Children fed formula lacking vitamin B6 show abnormal EEG seizures.Treatment with vitamin B6 can correct abnormalities of the electroencephalogram.Adults fed diets low in vitamin B6 for three to four weeks have also presented electroencephalographic abnormalities.

Studies in animals receiving vitamin B6 deficient intake showed that the offspring of rats deficient in this vitamin had alterations in fatty acid concentrations in the cerebellum and brain. Other changes were observed in nerve cells are low concentrations of alpha-aminobutyric acid and alteration of the amino acid concentration. These observations point out the need for an adequate intake of vitamin B6 for nervous system development.

The intake of vitamin B6 has a significant impact on immune function. In animal and human studies have found that a low intake of vitamin B6 is associated with immune disorders.

The production of interleukin-2 (IL-2) and lymphocyte proliferation are decreased in humans with vitamin B6.

Pyridoxal phosphate binds to the steroid receptors. In one of the binding sites, pyridoxal phosphate inhibits steroid receptor binding to DNA.

Vitamin B6 is stored primarily in liver and to a lesser extent in muscle and brain.

The total body reservoir of vitamin B6 has been estimated at 1.000 mol, of which 800 to 900 mol are present in muscle.

The replacement of pyridoxal phosphate in plasma has been associated with a dual-compartment model and has been estimated that the slow turnover of the stored portion occurs in 25 to 33 days.

The biological half-life of pyridoxine appears to be from 15 to 20 days, the liver is oxidized to pyridoxal pyridoxic acid, which is excreted in the urine.

Cyanocobalamin (Vitamin B12): The cobalamins are bound with high affinity to glycoproteins present in all mammalian tissues. One of them is the intrinsic factor, which is necessary in order to perform the normal absorption of vitamin B12.

Other glycoproteins are haptocorrinas (Hc, also called R binders, TC I and III) and transcobalamin II (TC II). Transcobalamin II binds to vitamin B12 in the cells of the terminal ileum and transported by plasma cells in the body.

Intrinsic factor is secreted by gastric parietal cells, but is also present in the cells of the fund, in antral G cells of the gastric mucosa and salivary glands.

For cobalamins bind to intrinsic factor and TC II requires a realignment of its binding to Co-N, this implies that both intrinsic factor as the TC II can not join the corrinoids cobalamínicos not.

In the stomach, vitamin B12 from the diet is liberated from its union with other organic compounds through the action of gastric acid and pepsin. The vitamin, which is predominantly methylcobalamin (MCB) and adenosylcobalamin (AdoCb), then joins the haptocorrinas.

Up to 0.2% of total body cobalamin deposit per day is excreted in the bile and is bound to haptocorrin. Also, apoptosis of intestinal mucosal cells containing cobalamin occurs at constant speed.

Partial proteolytic removal of cobalamin from haptocorrin and subsequent resorption of the receptor for cobalamin in the terminal ileum enterocyte may constitute the enterohepatic cycle of vitamin B12 when the amounts of vitamin B12 are greater than 1.0 mg, per day.

This may explain why the absorption of vitamin B12 occurs specifically at the end of the ileum 60 cm.

Once inside the cell of the ileum by a mechanism of endocytosis, cobalamin is released and the intrinsic factor is degraded by separate mechanisms that are related to the acidic region prelisosomal. The absorbed cobalamin is converted to methylcobalamin and adenosylcobalamin, probably within the mitochondria of the cell of the ileum.

In humans, 90% of cobalamin is bound to circulating transcobalamin I wherein has a half life of 9.3 to 9.8 days. The cobalamin bound to TC I is probably the only available form of vitamin B12 is stored in liver cells and the reticuloendothelial system.

The total content of vitamin B12 in the body of adults is 3 to 5 mg, of which 50% was found in the liver. The adenosylcobalamin constitutes over 70% of cobalamin in the liver, erythrocytes, brain and kidney, while methylcobalamin formed only 1 to 3%.

The plasma cobalamin is mainly methylcobalamin (60-80%), the remainder to hydroxocobalamin and adenosylcobalamin.

Excretion of cobalamin occurs through a process of apoptosis in the gastrointestinal tract, kidney and skin. This is an exceedingly slow process, since in cases of total gastrectomy, which reduces the absorption of cobalamin, virtually zero, only a deficiency of cobalamin enough to produce megaloblastic anemia after a period of 4 to 7 years. This is due to enterohepatic circulation.

In B12 cells functions as a coenzyme for methylmalonyl-CoA and methionine synthetase.

Methionine synthetase provides a junction between two important metabolic processes: the synthesis of DNA and RNA purines and pyrimidines. Another function of this enzyme is to act as a keeper for the entry of folate into cells.

Unlike what was thought a few years ago, the agency has no way of controlling the effects of vitamin B12 deficiency, so lack results in a series of complications which are distinguished which may have an association possible and which have a well defined. Among those with a definite association is megaloblastic anemia and neuropathy associated with vitamin B12 deficiency and a possible association are formation of atheroma that can cause thrombosis, cerebral vascular disease and peripheral neural tube defects and hepatic steatosis.

In particular, the neuropathy associated with vitamin B12 deficiency is related to changes in the rate of methylation. When the methionine synthase is inhibited due to vitamin B12 deficiency, occurs an increase of homocysteine and adenosylhomocysteine, which impairs the synthesis of methionine and adenosylmethionine, causing reduction in the rate of methylation, thishypomethylation status impairs the synthesis of myelin basic protein.

Organs like liver and kidney may remetilar homocysteine to methionine by a methyltransferase produce, however, this enzyme is not available in the brain.

CONTRAINDICATIONS: Hypersensitivity to the components of the formula.

The administration of any compound stimulating activity on hematopoiesis is contraindicated in polycythemia vera.

PRECAUTIONS: The administration of megadoses of pyridoxine has been associated with the presentation of neuropathic syndromes, which reversed upon discontinuation of treatment.

Use in Pregnancy and lactation: This product contains benzyl alcohol, so it should not be used during pregnancy or lactation or in newborns.

ADVERSE REACTIONS: Adverse reactions include burning at the site of application, can be seen rarely hypersensitivity reactions (in people susceptible to the components of the formula) consisting of respiratory distress, pruritus, abdominal pain and shock.

Some of these reactions can occur after prolonged application.

It has been reported the occurrence of peripheral neuropathy with prolonged administration of pyridoxine.

Other adverse effects include gastrointestinal disorders, folic acid deficiency, and children hypotonia and respiratory distress, in addition to skin reactions.

The administration of B vitamins for the treatment of megaloblastic anemia may mask a picture of polycythemia vera.

DRUG INTERACTIONS AND OTHER GENDER: Although the clinical significance is unknown, it has been reported that thiamine may increase the effect of neuromuscular blocking agents. Pyridoxine hydrochloride reverses the therapeutic effects of levodopa.

This investment can be reversed by concomitant administration of levodopa carbodopa.

Pyridoxine hydrochloride should not be administered at doses of 5 mg daily to patients receiving levodopa alone.

In a study that received 200 mg of pyridoxine daily for a month, there was approximately 50% reduction in serum concentration of phenobarbital and phenytoin, as well as interactions with hydralazine, cycloserine and penicillamine.

The simultaneous administration of pyridoxine and isoniazid or oral contraceptives may increase pyridoxine requirements.

Concomitant administration of pyridoxine and amiodarone can increase photosensitivity reactions induced by the latter.

The absorption of vitamin B12 in the gastrointestinal tract may be decreased by aminoglycosides (by mouth, such as neomycin), colchicine, potassium preparations extended release aminosalicylic acid and its salts, anticonvulsants (phenytoin, phenobarbital, primidone), irradiation cobalt in the small intestine, and excessive alcohol intake for more than two weeks.

In vitro, ascorbic acid can destroy substantial amounts of vitamin B12 and intrinsic factor and this possibility should be considered when giving large doses of ascorbic acid within the first hour was orally administered vitamin B12.

It has been reported that prednisone increases the absorption of vitamin B12 and intrinsic factor secretion in some patients with pernicious anemia, but not in patients with partial or total gastrectomy.

The clinical significance of these findings is unknown. Concomitant administration of chloramphenicol and vitamin B12 may antagonize hematopoietic response of vitamin B12 in patients receiving both drugs, so it must be carefully monitored and should be considered alternate antimicrobials.

Some data show that colestipol can bind to intrinsic factor-cyanocobalamin complex so that concomitant administration of this compound can reduce the bioavailability of preparations based on vitamins and minerals.

In one study found that treatment with omeprazole for two weeks until 90% can reduce the absorption of protein-bound cyanocobalamin. Therefore when required cyanocobalamin supplementation in patients receiving omeprazole should be preferred parenteral administration. A similar effect was observed with ranitidine and cimetidine, but these changes were due apparently to an alteration of intrinsic factor.

It has been reported that ascorbic acid, even at low doses, can destroy more than 80% of cyanocobalamin in foods, which does not occur with parenteral administration of vitamin B12.

CHANGES IN RESULTS OF LABORATORY TESTS: It is reported that pyridoxine may produce a false-positive reaction urobilinogen when using the Ehrlich reagent.

PRECAUTIONS IN RELATION TO EFFECTS OF CARCINOGENESIS, MUTAGENESIS, Impairment of Fertility: In animal studies there are no reports of carcinogenicity, mutagenicity, teratogenicity or impaired fertility.

DOSAGE AND ADMINISTRATION: Intramuscular deep. 2 ml (one vial or prefilled syringe) every 24 or 48 hours.

REPRESENTATIONS AND MANAGEMENT Overdosage: With respect to thiamine no danger of overdose.

About pyridoxine, although as has been considered relatively nontoxic, long-term (eg 2 months or more) administration of megadoses of pyridoxine (eg 2 g or more per day) can cause sensory neuropathy or neuropathic syndromes. The pathogenesis and biochemical basis of pyridoxine-induced neurotoxicity have not been determined. This suggested that sensory syndrome caused by megadoses of pyridoxine may be a vulnerability of neurons in the dorsal root ganglion.

Have been observed, rarely, some adverse neurological level due to chronic administration of approximate dose of 500 mg of pyridoxine. Although the causal relationship was not established pyridoxine, reported a case of sensory neuropathy with subsequent axonal degeneration in a patient who received a single dose of 10 g of pyridoxine intravenously.

Manifestations: There are reports of deterioration of position sense and vibration of the distal limbs, and progressive ataxia in several patients. The sense of touch, temperature and pain were less affected, and no generalized weakness and neither condition of deep reflexes.

Nerve conduction studies and somatosensory captured responses indicative of dysfunction of the distal ends of peripheral sensory nerves. Nervous tissue biopsies showed no axonal damage. Upon discontinuation of pyridoxine, neurologic dysfunction gradually improved and after a follow-up period, patients recover satisfactorily. As for vitamin B12 is no danger of overdose.

PRESENTATIONS:

1.000 Neurobion Glaspak is shown in box with 5 vials with 2 ml solution each, and glass syringes with 5 sterile disposable needles.

Neurobion Hypak 1.000, 5.000 and 10.000 Hypak Hypak are presented in box with 5 pre-filled syringes, disposable, 2 ml solution for injection and 5 each disposable sterile needles.

STORAGE RECOMMENDATIONS:

Store at a temperature not higher than 30 ° C.

Protect from light.

Vitamins and Minerals

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NEUROBION 10 000 HYPACK 5 INJECTIONS

Vitamins and Minerals

Comments and ratings: NEUROBION 10 000 HYPACK 5 INJECTIONS

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NEUROBION 10 000 HYPACK 5 INJECTIONS