NURAMINE FORTE INJECTION

Mechanism of action

Cyanocobalamin serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase is involved in the degradation of propionate, crucial for fat and protein metabolism. The lack of vitamin B12 results in the accumulation of methylmalonyl CoA, contributing to neurological manifestations. Additionally, it is vital for the synthesis of methionine from homocysteine, and its deficiency can lead to functional folate deficiency, which impacts red blood cell formation.

Pharmacodynamics

Cyanocobalamin corrects vitamin B12 deficiency and alleviates symptoms and laboratory abnormalities associated with pernicious anemia, such as megaloblastic indices, gastrointestinal lesions, and neurological damage. It is essential for growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. The drug significantly impacts fat and carbohydrate metabolism, as well as protein synthesis. Rapidly dividing cells, such as those in the bone marrow, have a high demand for vitamin B12. Parenteral administration of cyanocobalamin can quickly reverse the anemia and gastrointestinal symptoms of vitamin B12 deficiency, while also preventing the progression of related neurological damage.

Pharmacokinetics

Cyanocobalamin is absorbed in the intestine, primarily in the ileum, via specific transport mechanisms that may be impaired in individuals with intrinsic factor deficiency (as seen in pernicious anemia). Once absorbed, it is widely distributed in body tissues, with significant concentrations found in the liver, kidneys, and heart. The vitamin is stored in the liver, where it can be released into circulation as needed. Cyanocobalamin undergoes conversion to its active forms, methylcobalamin and adenosylcobalamin, which are utilized in various metabolic processes. The elimination half-life is variable, but it is generally excreted via urine as metabolites

Adverse effects

• Abdominal distension
• Decreased appetite
• Flatulence
• Nausea

Interactions

• Folic acid may interact with cyanocobalamin, especially in cases of megaloblastic anemia caused by folate deficiency.

Precautions

• Should not be given alone for pernicious anemia.
• Use caution in patients with Leber's disease, as it may worsen optic atrophy.

Pregnancy

Cyanocobalamin is essential during pregnancy as it helps prevent neural tube defects. It is advised that females of childbearing potential take 5 mg of folic acid daily before conception and throughout pregnancy.

Breast-feeding

Cyanocobalamin is generally considered safe during breastfeeding, but it is advised to monitor the infant for any adverse effects.

Storage

Store in a cool, dry place, away from direct sunlight. Protect from moisture.

Formulations

• Tablet: 1000 micrograms
• Tablet: 500 micrograms
• Tablet: 100 micrograms
• Oral solution: 50 micrograms per ml
• Solution for injection: 1000 micrograms per ml

Indications

• Vitamin B6 deficiency
• Peripheral neuropathy associated with isoniazid
• Prophylaxis of vitamin B6 deficiency
• Essential hypertension
• Altered immune response due to vitamin B6 deficiency

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: Refer to the BNF for specific adult dosing recommendations based on the condition being treated.

Mechanism of action

Pyridoxine is converted in the body to its active form, pyridoxal 5'-phosphate (PLP). PLP acts as a coenzyme in various enzymatic reactions, facilitating the metabolism of amino acids, the synthesis of neurotransmitters such as serotonin, dopamine, and GABA, and the production of hemoglobin. It is essential for the proper functioning of enzymes involved in these metabolic pathways.

Pharmacodynamics

Pyridoxine has been shown to exhibit several pharmacodynamic effects, including the reduction of blood pressure in individuals with essential hypertension. It may also influence lipid metabolism, as studies indicate that it can lower total cholesterol while increasing HDL-cholesterol levels. Additionally, vitamin B6 plays a vital role in immune function, with deficiency linked to impaired lymphocyte function and antibody responses.

Pharmacokinetics

Pyridoxine is absorbed in the intestine and is widely distributed throughout the body, particularly in the liver, where it is phosphorylated to its active form, pyridoxal 5'-phosphate. The elimination half-life varies, but excess vitamin B6 is typically excreted in urine as pyridoxine and its metabolites. The bioavailability of pyridoxine can be influenced by dietary factors and the presence of certain medications.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Headache
• Drowsiness
• Peripheral neuropathy (with high doses)

Interactions

• Isoniazid may reduce plasma levels of vitamin B6
• Levodopa may have reduced effectiveness when administered with vitamin B6

Precautions

• Use cautiously in patients with renal impairment
• High doses should be avoided to prevent neuropathy

Pregnancy

Vitamin B6 is generally considered safe during pregnancy, and it is often used to alleviate nausea and vomiting associated with morning sickness.

Breast-feeding

Vitamin B6 is excreted in breast milk but is considered safe for breastfeeding mothers, as it is essential for infant development.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solution
• Injectable form

Indications

• Thiamine deficiency
• Beriberi
• Wernicke-Korsakoff syndrome
• Supplementation in chronic alcoholism
• Supportive therapy in metabolic disorders

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in pediatric populations.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Thiamine functions as a coenzyme in the form of thiamine pyrophosphate (TPP) for several key enzymes involved in carbohydrate metabolism. These include pyruvate dehydrogenase, which converts pyruvate into acetyl-CoA, and alpha-ketoglutarate dehydrogenase, which is involved in the citric acid cycle. Through these actions, thiamine plays a vital role in energy production and the synthesis of neurotransmitters.

Pharmacodynamics

Thiamine is involved in several metabolic pathways, including carbohydrate metabolism and the synthesis of neurotransmitters. It is essential for nerve function and plays a protective role in cardiac health. Adequate thiamine levels are crucial for the prevention of metabolic disorders such as beriberi and Wernicke-Korsakoff syndrome, which are associated with thiamine deficiency.

Pharmacokinetics

Thiamine is rapidly absorbed from the gastrointestinal tract, with peak plasma levels occurring within 1 to 2 hours after oral administration. It is widely distributed in body tissues, particularly in the liver, heart, and skeletal muscle. The body does not store significant amounts of thiamine, and excess is excreted in urine. The half-life of thiamine is approximately 1 to 2 hours. Its bioavailability can be affected by factors such as gastrointestinal health and the presence of other nutrients.

Adverse effects

• Hypersensitivity reactions
• Nausea
• Vomiting
• Diarrhea
• Irritation at the injection site

Interactions

• Chloramphenicol may inhibit the action of thiamine
• Some diuretics may increase thiamine excretion

Precautions

• Use with caution in patients with renal impairment
• Monitor patients with thiamine deficiency due to alcoholism
• Assess for hypersensitivity to thiamine or any excipients in the formulation

Pregnancy

Thiamine is generally considered safe for use during pregnancy and is often required to meet increased nutritional demands.

Breast-feeding

Thiamine is excreted in breast milk, but it is considered safe to use while breastfeeding.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Tablets
• Injectable solution
• Oral suspension

Mechanism of action

Vitamin B12 serves as a cofactor for _methionine synthase_ and _L-methylmalonyl-CoA mutase_ enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to _succinyl-CoA_ in the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin. In tissues, vitamin B12 is required for the synthesis of _methionine_ from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency,. This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form _methionine_ and _tetrahydrofolate_. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

Pharmacodynamics

**General effects** Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12. **Parenteral cyanocobalamin effects** The parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition. **Nasal spray effects** In 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L).

Mechanism of action

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

Pharmacodynamics

Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.