AVAVITE VITAMIN SUPPLEMENT

Indications

• Vitamin K deficiency
• Coagulation disorders due to vitamin K deficiency
• Reversal of anticoagulation in patients on warfarin therapy
• Neonatal prophylaxis of vitamin K deficiency bleeding

Dosage

Adults: For adults, the typical dosage is 1-5 mg administered orally or via slow intravenous injection. Dosing may be adjusted based on clinical response and INR levels.

Mechanism of action

Vitamin K acts as a cofactor for the enzyme gamma-carboxylase, which catalyzes the carboxylation of specific glutamic acid residues on clotting factors II (prothrombin), VII, IX, and X. This carboxylation allows these factors to bind calcium ions, which is essential for their activation and subsequent role in the coagulation cascade. Additionally, vitamin K is involved in carboxylating matrix proteins in chondrocytes, possibly influencing bone density and vascular calcification.

Pharmacodynamics

Phytomenadione is indicated in the management of coagulation disorders resulting from vitamin K deficiency. It promotes the hepatic biosynthesis of prothrombin and other clotting factors, restoring normal clotting function. Its long duration of action and wide therapeutic index make it a safe option for patients requiring vitamin K supplementation, but monitoring of prothrombin time is essential during therapy. Hypersensitivity reactions may occur, especially with parenteral administration.

Pharmacokinetics

Phytomenadione is absorbed in the intestine and transported in the lymphatic system. It is then stored in the liver and released into circulation as needed for clotting factor synthesis. Vitamin K has a long half-life, allowing for sustained action, and is cycled in the body, contributing to its prolonged effects. The elimination occurs primarily through the hepatic pathway, and caution is advised in patients with hepatic impairment.

Contra-indications

• Hypersensitivity to phytomenadione or any of its excipients
• Severe hepatic impairment
• Hyperbilirubinaemia in neonates
• Known risk of hemolytic anemia in newborns

Adverse effects

• Anaphylactoid reactions (especially with intravenous use)
• Hypersensitivity reactions
• Flushing
• Rash
• Gastrointestinal disturbances

Interactions

• Anticoagulants (e.g., warfarin) - may require dose adjustment
• Cholestyramine - may reduce absorption of vitamin K
• Mineral oil - may interfere with absorption
• Antibiotics (e.g., cephalosporins) - may affect vitamin K synthesis by gut flora

Precautions

• Use with caution in patients with G6PD deficiency due to risk of hemolysis
• Monitor INR closely in patients with hepatic impairment
• Use intravenous preparations slowly to avoid vascular collapse
• Caution in elderly patients due to altered pharmacokinetics

Pregnancy

Use only if potential benefit outweighs risk, especially in late pregnancy due to risk of neonatal hemolytic anemia.

Breast-feeding

Present in breast milk; caution is advised if large doses are administered.

Storage

Store at room temperature, away from light and moisture. Protect from freezing.

Formulations

• Capsules (200 units, 400 units)
• Oral solutions
• Tablets (10 mg)
• Injectable solution for intravenous use

Indications

• Vitamin B6 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Idiopathic sideroblastic anaemia
• Prevention of penicillamine-induced neuropathy in Wilson's disease
• Metabolic diseases such as cystathioninuria and homocystinuria
• Premenstrual syndrome

Mechanism of action

Pyridoxine hydrochloride is converted in the body to pyridoxal phosphate, which is the active form of vitamin B6. It serves as a cofactor for more than 100 enzymatic reactions, particularly those involved in the metabolism of amino acids, the synthesis of neurotransmitters (such as serotonin, dopamine, and gamma-aminobutyric acid), and the production of hemoglobin. Its role in neurotransmitter synthesis makes it crucial for normal brain function and mood regulation.

Pharmacodynamics

Pyridoxine hydrochloride exerts its effects by facilitating the conversion of amino acids into neurotransmitters and is involved in the synthesis of heme. It impacts the metabolism of tryptophan to serotonin and is essential for the production of norepinephrine and gamma-aminobutyric acid, which are vital for proper neurological function. Deficiency of vitamin B6 can lead to neurological symptoms, including peripheral neuropathy and cognitive disturbances.

Pharmacokinetics

Pyridoxine hydrochloride is readily absorbed from the gastrointestinal tract. It is primarily metabolized in the liver, where it is converted to its active form, pyridoxal phosphate. The elimination half-life of pyridoxine is approximately 15-20 days, and it is excreted primarily through the urine. Renal impairment may affect the metabolism and excretion of pyridoxine, necessitating dose adjustments.

Contra-indications

• Hyperkalaemia
• Severe liver damage

Adverse effects

• Peripheral neuritis
• Hepatitis
• Hypoglycaemia
• Urine discolouration

Interactions

• Potassium aminobenzoate
• Isoniazid

Precautions

• Caution in renal impairment (increased risk of hyperkalaemia)
• Interrupt treatment during periods of low food intake (such as fasting, anorexia, and nausea) to reduce risk of hypoglycaemia
• Monitor liver function tests monthly during high-dose therapy

Pregnancy

Manufacturer advises avoiding use in pregnancy due to potential risk of birth defects; however, no adverse effects have been reported at normal dietary levels.

Breast-feeding

Theoretical risk of toxicity in infants if mothers take large doses.

Storage

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

Formulations

• Pyridoxine hydrochloride 10 mg tablets
• Pyridoxine hydrochloride 20 mg tablets
• Pyridoxine hydrochloride 50 mg tablets
• Pyridoxine hydrochloride oral solution 20 mg per 1 ml

Indications

• Isolated carboxylase defects
• Defects of biotin metabolism
• Prevention of deficiency in complete biliary obstruction

Dosage

Children: Neonate: Initially 10 mg once daily, adjusted according to response; maintenance 5–20 mg daily. Child: Initially 10 mg once daily, adjusted according to response; maintenance 5–20 mg daily, higher doses may be required.

Adults: For adults, the dosing may vary based on the condition being treated. General guidance is to refer to the BNF for specific dosing recommendations.

Mechanism of action

Biotin acts as a coenzyme for carboxylase enzymes, facilitating critical metabolic processes including gluconeogenesis, fatty acid synthesis, and amino acid catabolism.

Pharmacodynamics

Biotin is essential for the carboxylation of substrates in metabolic pathways, influencing energy metabolism and the synthesis of important biomolecules. It supports normal growth and development.

Pharmacokinetics

Biotin is absorbed in the intestine and is widely distributed in body tissues. It is not stored in large amounts, with excess being excreted in urine. The half-life and specific pharmacokinetic parameters can vary based on individual metabolism and dietary intake.

Adverse effects

• Rough skin
• Dry hair
• Enlarged liver
• Increases in erythrocyte sedimentation rate
• Increased serum calcium
• Increased serum alkaline phosphatase concentration

Precautions

• Excessive doses may be teratogenic
• High levels of vitamin A may cause birth defects

Pregnancy

No information available.

Breast-feeding

No information available.

Formulations

• Tablet
• Oral suspension
• Oral solution
• Solution for injection

Indications

• Papulopustular rosacea
• Inflammatory acne vulgaris

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: For papulopustular rosacea, apply daily for up to 4 months. The treatment course may be repeated; discontinue if no improvement is observed after 3 months. For inflammatory acne vulgaris, apply twice daily, reduced to once daily or alternate days if irritation occurs.

Mechanism of action

Nicotinamide exhibits anti-inflammatory effects by inhibiting the release of pro-inflammatory cytokines and enhancing the barrier function of the skin. It is also involved in the NAD salvage pathway, which is essential for maintaining cellular energy levels and promoting cell repair mechanisms. Additionally, nicotinamide contributes to the synthesis of coenzymes involved in metabolic processes, including the conversion of niacin into NAD+.

Pharmacodynamics

Nicotinamide is known for its ability to improve skin hydration and reduce transepidermal water loss. It has been shown to decrease the appearance of acne lesions and rosacea by modulating inflammatory responses and accelerating cell turnover. Its antioxidant properties also help to protect the skin from oxidative stress and UV damage.

Pharmacokinetics

When applied topically, nicotinamide is absorbed through the skin layers, with minimal systemic absorption. Its peak plasma concentrations are generally low, and the drug has a half-life that varies depending on the route of administration. The metabolism of nicotinamide occurs primarily in the liver, where it is converted into its active forms, including NAD+. The elimination route is via the kidneys, with metabolites excreted in urine.

Contra-indications

• Pregnancy
• Severe acne involving large areas
• Severe skin reactions

Adverse effects

• Sunburn
• Skin reactions (common or very common)
• Cheilitis
• Eyelid oedema
• Flushing
• Dry skin
• Eye irritation
• Photosensitivity reactions
• Transient skin pigmentation changes

Interactions

• Clindamycin
• Topical retinoids
• Abrasive cleaners
• Comedogenic cosmetics

Precautions

• Avoid exposure to UV light, including sunlight and sunlamps
• Wash hands immediately after use
• Avoid contact with eyes and mucous membranes
• Use moisturizers to reduce the risk of skin irritation
• Discontinue treatment if severe irritation occurs

Pregnancy

Avoid use during pregnancy due to potential risks, as limited information is available regarding toxicity.

Breast-feeding

Amount of drug in milk after topical application is probably too small to be harmful; ensure infant does not come in contact with treated areas.

Storage

Store at room temperature away from moisture and light.

Formulations

• Cream
• Gel

Indications

• Vitamin B1 deficiency
• Wernicke-Korsakoff syndrome
• Beriberi
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Severe depletion or malabsorption of vitamins B and C

Dosage

Adults: For vitamin deficiency: 25–100 mg daily. For severe deficiency: 200–300 mg daily in divided doses. For

Mechanism of action

Thiamine functions primarily as a precursor for several phosphorylated active forms, which act as coenzymes in metabolic pathways. It reduces intracellular protein glycation by redirecting glycolytic flux and supports the synthesis of nucleic acids necessary for cell survival and proliferation. Additionally, thiamine has been shown to inhibit glucose-induced proliferation of endothelial cells, thus possibly playing a role in the modulation of vascular health.

Pharmacodynamics

Thiamine exhibits antioxidant properties and contributes to erythropoiesis, cognitive function, and mood regulation. It has protective effects against oxidative stress, particularly in neuronal tissues, where deficiency can lead to neuronal death due to increased free radical production. Thiamine also modulates glucose metabolism, influencing smooth muscle cell proliferation and potentially impacting the progression of atherosclerosis.

Pharmacokinetics

Thiamine is rapidly absorbed from the gastrointestinal tract, primarily in the jejunum, and is distributed throughout the body, with higher concentrations found in the liver, heart, and brain. It is excreted in urine, and its half-life is relatively short. The vitamin is converted into active forms within tissues, including thiamine diphosphate (TDP), which is the coenzyme form involved in carbohydrate metabolism. The body does not store significant amounts of thiamine, making regular dietary intake essential.

Adverse effects

• Allergic reactions
• Anaphylaxis (rare)
• Gastrointestinal disturbances

Precautions

• Facilities for treating anaphylaxis should be available when parenteral thiamine is administered
• Use with caution in patients with a history of hypersensitivity to thiamine

Pregnancy

Thiamine crosses the placenta but no adverse effects have been reported. Information regarding high doses is limited.

Breast-feeding

Severely thiamine-deficient mothers should avoid breast-feeding as thiamine is present in breast milk.

Storage

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

Formulations

• Thiamine hydrochloride 20 mg/ml oral solution
• Thiamine hydrochloride 50 mg tablets
• Thiamine hydrochloride 100 mg modified-release tablets
• Thiamine hydrochloride oral suspension

Indications

• Vitamin B12

Mechanism of action

Cyanocobalamin serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is vital for the synthesis of purines and pyrimidines necessary for DNA, while L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA, a key step in fat and protein metabolism. The lack of vitamin B12 leads to the accumulation of methylmalonyl CoA, which is associated with neurological symptoms of deficiency. Additionally, vitamin B12 is required for synthesizing methionine from homocysteine, which is crucial for many biological processes.

Pharmacodynamics

Cyanocobalamin corrects vitamin B12 deficiency and alleviates symptoms and laboratory abnormalities linked to pernicious anemia, such as megaloblastic indices and neurological damage. It supports growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. This vitamin also plays a significant role in the metabolism of fats, carbohydrates, and proteins. Rapidly dividing cells, including epithelial and bone marrow cells, have a high demand for vitamin B12. Parenteral administration effectively reverses megaloblastic anemia and gastrointestinal symptoms, while intranasal routes can maintain serum vitamin B12 levels in stabilized patients.

Pharmacokinetics

Cyanocobalamin is well-absorbed when administered parenterally and can be stored in the liver, where it is released as needed. The pharmacokinetics can vary based on the route of administration, with parenteral forms providing rapid increases in serum concentrations. After absorption, it is transported in the bloodstream bound to transcobalamin II. The half-life of vitamin B12 can be several days, depending on the individual's status and the presence of deficiency.

Adverse effects

• Hypokalemia
• Allergic reactions
• Rash
• Itching
• Diarrhea

Interactions

• Chloramphenicol may inhibit the therapeutic effects of vitamin B12
• Anticonvulsants may affect vitamin B12 metabolism

Precautions

• Monitor potassium levels in patients with severe deficiency
• Use with caution in patients with Leber's disease
• Assess for potential allergies to cobalt or vitamin B12

Pregnancy

Cyanocobalamin is generally considered safe in pregnancy, but caution is advised. Adequate vitamin B12 levels are important for fetal development.

Breast-feeding

Cyanocobalamin is safe for use during breastfeeding, as it is excreted in breast milk in small amounts.

Storage

Store in a cool, dry place away from light. Once opened, use within a specified period as recommended by the manufacturer.

Formulations

• Intramuscular injection
• Oral tablets
• Nasal spray

Mechanism of action

Folic acid is biochemically inactive until it is converted into active forms, primarily tetrahydrofolic acid and methyltetrahydrofolate, by the enzyme dihydrofolate reductase (DHFR). These active forms are essential for maintaining normal erythropoiesis, synthesizing nucleic acids, interconverting amino acids, and generating formate. They participate in critical one-carbon transfer reactions necessary for DNA synthesis and methylation processes. Folic acid, in conjunction with vitamin B12, helps normalize elevated homocysteine levels by facilitating its remethylation to methionine, a process that is crucial for various metabolic pathways.

Pharmacodynamics

Folic acid is an essential cofactor for enzymes involved in nucleic acid synthesis and amino acid metabolism. It is particularly significant in preventing megaloblastic anemia, which arises from impaired DNA synthesis due to folate deficiency. The synthesis of thymidylate, necessary for DNA formation, is directly influenced by folate availability. Folic acid's role is especially crucial during periods of rapid cellular division, and it has protective effects against certain cancer developments. As humans cannot synthesize folic acid endogenously, adequate dietary intake is essential for maintaining normal physiological functions.

Pharmacokinetics

Folic acid is absorbed in the small intestine and is then converted into its active forms within the body. The bioavailability of folic acid is influenced by factors such as food composition and the presence of certain gastrointestinal conditions. Once absorbed, it is transported in the bloodstream, mainly as 5-methyltetrahydrofolate. The distribution of folate occurs within various tissues, with significant

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Skin rash
• Altered sleep patterns

Interactions

• Anticonvulsants may reduce the effectiveness of folic acid
• Methotrexate may interfere with folic acid metabolism
• Trimethoprim-sulfamethoxazole can enhance the effects of folic acid deficiency

Precautions

• Monitor for signs of anemia in patients with malabsorption syndromes
• Use cautiously in patients with a history of hypersensitivity to folic acid
• Assess for vitamin B12 deficiency before initiating treatment, as folic acid can mask symptoms

Pregnancy

Folic acid is essential during pregnancy to prevent neural tube defects and support fetal development. Supplementation is recommended before conception and during the first trimester.

Breast-feeding

Folic acid passes into breast milk, and adequate maternal intake is important to ensure sufficient levels for the nursing infant.

Storage

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

Formulations

• Tablets
• Oral solutions
• Injectable forms

Mechanism of action

Excessive palmitoylcarnitine formation and exhausted L-carnitine stores lead to energy depletion, which, along with attenuated acetylcholine synthesis and oxidative stress, are main mechanisms behind palmitate-induced neuronal loss. High levels of palmitate exposure are suggested to contribute to diabetic neuropathy and gastrointestinal dysregulation. Additionally, palmitate negatively regulates acetyl-CoA carboxylase, thereby preventing further palmitate generation.

Pharmacodynamics

Palmitate is the first fatty acid generated during lipogenesis and serves as a precursor for the synthesis of longer fatty acids. The presence of palmitate inhibits acetyl-CoA carboxylase, reducing the conversion of acetyl-ACP to malonyl-ACP, which subsequently decreases the synthesis of new palmitate. This feedback mechanism is crucial for maintaining lipid homeostasis within the body.

Pharmacokinetics

Palmitate is absorbed from dietary sources and can also be synthesized endogenously in the liver and adipose tissue. Once in circulation, it is transported via chylomicrons or albumin. The metabolism of palmitate occurs primarily in the mitochondria through fatty acid oxidation, generating acetyl-CoA, which can enter the citric acid cycle for energy production. The overall kinetics of palmitate are influenced by dietary intake, metabolic demand, and hormonal regulation.

Pregnancy

Palmitate is classified as a category C drug. Animal reproduction studies have not been conducted, and there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There are no data on the excretion of palmitate in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep the container tightly closed.

Formulations

• Palmitate 500 mg softgel
• Palmitate 1000 mg softgel

Indications

• Dry skin
• Wound healing
• Dermatitis
• Eczema
• Skin irritation

Dosage

Children: For paediatric patients, refer to the BNF for Children for specific dosing recommendations.

Adults: For topical use, apply as needed to affected areas, typically 1-2 times daily.

Mechanism of action

Panthenol is enzymatically converted to pantothenic acid, which is a vital component of Coenzyme A. This cofactor is essential for numerous enzymatic reactions, particularly in protein metabolism within epithelial tissues. Additionally, dexpanthenol enhances fibroblast proliferation and accelerates re-epithelialization, facilitating wound healing and providing a protective barrier.

Pharmacodynamics

Pantothenic acid serves as a precursor to coenzyme A, which is crucial for the transfer of acetyl groups in various metabolic processes. It is involved in the synthesis of acetylcholine, a neurotransmitter that plays a vital role in the parasympathetic nervous system. Adequate levels of acetylcholine are necessary for normal intestinal function, including peristalsis, and a deficiency may lead to gastrointestinal issues such as adynamic ileus.

Pharmacokinetics

The pharmacokinetics of panthenol include its absorption, distribution, metabolism, and excretion. When applied topically, dexpanthenol is readily absorbed and metabolized into pantothenic acid. The systemic absorption is generally low when used in topical formulations, minimizing the risk of systemic side effects. The retention of moisture and enhancement of epithelial barrier function are key therapeutic benefits.

Pregnancy

Panthenol is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare provider before use.

Breast-feeding

Panthenol is considered safe for use during breastfeeding; however, it is recommended to consult a healthcare professional.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Topical solution

Indications

• Vitamin B6 deficiency
• Peripheral neuropathy associated with isoniazid therapy
• Supplementation in specific dietary deficiencies

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidance.

Adults: Refer to the BNF for specific dosing details, typically 10-50 mg daily for deficiency.

Mechanism of action

Pyridoxine, mainly in its active form pyridoxal 5'-phosphate, is involved in numerous biochemical reactions, including amino acid metabolism, glycogen breakdown, nucleic acid synthesis, and the production of key neurotransmitters. It aids in the synthesis of hemoglobin and sphingolipids, and its deficiency can impair several physiological processes, including immune response and vascular health.

Pharmacodynamics

Pyridoxine is utilized for the prevention and treatment of vitamin B6 deficiency, particularly in individuals undergoing treatment with isoniazid, which can deplete vitamin B6 levels. It may also have beneficial effects on blood pressure and lipid profiles, as studies have shown it can lower both systolic and diastolic blood pressure, inhibit platelet aggregation, and improve cholesterol levels. Additionally, it plays a role in enhancing immune function and protecting endothelial cells from injury.

Pharmacokinetics

Pyridoxine is rapidly absorbed from the gastrointestinal tract. It is transported to tissues where it is phosphorylated to its active form, pyridoxal 5'-phosphate. The vitamin is primarily excreted in urine as pyridoxine and its metabolites. Its half-life varies depending on the individual’s nutritional status and other factors. Adequate dietary intake is essential for maintaining optimal levels in the body.

Pregnancy

Pyridoxine is generally considered safe during pregnancy. However, high doses should be avoided unless specifically prescribed.

Breast-feeding

Pyridoxine is excreted in breast milk, but at normal dietary levels it is considered safe for breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Oral solution
• Injectable form

Indications

• Riboflavin deficiency
• Migraines (as adjunctive therapy)
• Certain skin and eye disorders (such as cataracts)
• Anemia (as supportive treatment)

Dosage

Children: Refer to authoritative resources for specific dosing guidelines.

Adults: Refer to authoritative resources for specific dosing guidelines.

Mechanism of action

Riboflavin acts as a precursor for the synthesis of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential cofactors in various enzymatic reactions. These cofactors are involved in redox reactions, aiding in the conversion of carbohydrates, fats, and proteins into energy. Riboflavin-dependent enzymes are crucial for the metabolism of amino acids and the electron transport chain in mitochondrial respiration.

Pharmacodynamics

Riboflavin exhibits various pharmacodynamic properties, including its involvement in the antioxidant defense system. It helps in regenerating glutathione, a critical antioxidant, thus protecting cells from oxidative stress. Furthermore, riboflavin is important for the synthesis of other B vitamins, such as niacin and pyridoxine, enhancing overall metabolic health and cellular function.

Pharmacokinetics

Riboflavin is readily absorbed from the gastrointestinal tract, primarily in the proximal small intestine. Its absorption can be influenced by the presence of food, with higher bioavailability when taken with meals. Once absorbed, riboflavin is distributed throughout the body, with significant concentrations found in the liver, kidneys, and heart. The vitamin is excreted via urine, and excess amounts are eliminated in a water-soluble form. The body maintains riboflavin homeostasis through a combination of dietary intake and renal excretion.

Adverse effects

• No known serious adverse effects.
• Mild gastrointestinal disturbances.
• Bright yellow discoloration of urine.

Precautions

• Use with caution in patients with an allergy to riboflavin or any of its components.

Pregnancy

Riboflavin is considered safe during pregnancy and is often included in prenatal vitamins.

Breast-feeding

Riboflavin is excreted in breast milk and is generally regarded as safe for breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solutions
• Powder for reconstitution

Indications

• Thiamine deficiency
• Wernicke's encephalopathy
• Beriberi
• Alcoholism-related complications
• Certain metabolic disorders

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: Refer to established clinical guidelines or BNF for specific dosing recommendations.

Mechanism of action

Thiamine is a coenzyme for several important enzymatic reactions, including the pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase. It is essential for converting carbohydrates into energy, facilitating the metabolism of glucose, and maintaining normal nerve function.

Pharmacodynamics

Thiamine deficiency leads to impaired carbohydrate metabolism, which can result in neurological and cardiovascular dysfunction. Supplementation with thiamine helps restore normal metabolic function and can alleviate symptoms associated with deficiency, such as Wernicke's encephalopathy and Beriberi. It also plays a role in the synthesis of neurotransmitters and in maintaining myelin integrity.

Pharmacokinetics

Thiamine is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is distributed throughout the body, primarily in the liver, kidneys, and heart. Thiamine is metabolized in the liver to its active form, thiamine pyrophosphate. It has a biological half-life of about 9-18 days and is excreted primarily in the urine. Excess thiamine is excreted, making toxicity rare.

Adverse effects

• Allergic reactions
• Hypersensitivity reactions
• Gastrointestinal disturbances

Interactions

• May interact with certain diuretics, leading to altered thiamine levels

Precautions

• Use with caution in patients with renal impairment
• Monitor patients with a history of thiamine deficiency

Pregnancy

Thiamine is considered safe during pregnancy, as it is an essential nutrient.

Breast-feeding

Thiamine is excreted in breast milk, but supplementation is generally considered safe for breastfeeding mothers.

Storage

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

Formulations

• Thiamine hydrochloride injection
• Thiamine hydrochloride oral tablets
• Thiamine hydrochloride oral solution

Indications

• Vitamin deficiency syndromes (e.g., scurvy for vitamin C deficiency, rickets for vitamin D deficiency)
• Support for immune function
• Antioxidant support
• Bone health maintenance
• Vision health
• Energy metabolism support

Dosage

Children: Refer to the BNF for Children for specific vitamin dosing guidelines, which depend on age and nutritional requirements.

Adults: Refer to specific vitamin guidelines as dosage varies significantly depending on the type of vitamin and individual needs.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for coenzymes in enzymatic reactions. For instance, B vitamins are involved in energy metabolism, while vitamins A, C, D, E, and K support various physiological functions including vision, antioxidant activity, calcium regulation, and blood clotting. Each vitamin has a unique mechanism of action based on its structure and role in the body.

Pharmacodynamics

Vitamins exert their effects at the cellular level, influencing metabolic pathways, gene expression, and immune responses. For example, vitamin D regulates calcium and phosphate homeostasis, while vitamin A is crucial for vision and immune function. Deficiencies in vitamins can lead to a range of disorders, highlighting their importance in maintaining health.

Pharmacokinetics

The pharmacokinetics of vitamins vary widely. Fat-soluble vitamins (A, D, E, and K) are stored in liver and adipose tissues and can be released into circulation as needed. Water-soluble vitamins (B-complex and C) are not stored and must be consumed regularly, with excess amounts excreted in urine. Absorption rates, half-lives, and distribution can also differ based on the specific vitamin and individual metabolic factors.

Interactions

• tretinoin+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Moderate (increases risk of toxicity)
• carbamazepine+vitamin: Unknown (decreases effects)
• cobicistat+vitamin: Unknown (increases exposure)
• vitamin D substances+digoxin: Unknown (increases risk of toxicity)
• idelalisib+vitamin: Unknown (increases exposure)
• clarithromycin+vitamin: Unknown (increases exposure)

Pregnancy

Consult healthcare professional before use. Vitamin supplementation during pregnancy should be carefully managed to avoid hypervitaminosis.

Breast-feeding

Consult healthcare professional before use. Some vitamins can pass into breast milk and may affect the infant.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept out of reach of children.

Formulations

• {'name': 'Vitamin A', 'form': 'Capsule', 'strength': '10000 IU'}
• {'name': 'Vitamin D', 'form': 'Tablet', 'strength': '1000 IU'}
• {'name': 'Vitamin E', 'form': 'Softgel', 'strength': '400 IU'}

Mechanism of action

Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids. In human tissues biotin is a cofactor for the enzymatic carboxylation of four substrates: pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA. As such, it plays an important role in both carbohydrate and fat metabolism. Carbon dioxide fixation occurs in a two-step reaction, the first involving binding of carbon dioxide to the biotin moiety of the holoenzyme, and the second involving transfer of the biotin-bound carbon dioxide to an appropriate acceptor. Biotin functions in carbon dioxide fixation reactions in intermediate metabolism, transferring the carboxyl group to acceptor molecules. It acts similarly in decarboxylation reactions. Biotin is essential in human metabolism for its part in the previously described enzymatic steps, in catalyzing deamination of amino acids, and in oleic acid synthesis. Biotin is a cofactor for the enzymatic carboxylation of pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA, and, therefore, plays an important role in carbohydrate and fat metabolism. Protein folding in the endoplasmic reticulum (ER) depends on Ca2+; uptake of Ca2+ into the ER is mediated by sarco/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3). The 5'-flanking region of the SERCA3 gene (ATP2A3) contains numerous binding sites for the transcription factors Sp1 and Sp3. Biotin affects the nuclear abundance of Sp1 and Sp3, which may act as transcriptional activators or repressors. Here we determined whether biotin affects the expression of the SERCA3 gene and, thus, protein folding in human lymphoid cells. Jurkat cells were cultured in media containing 0.025 nmol/L biotin (denoted "deficient") or 10 nmol/L biotin ("supplemented"). The transcriptional activity of the full-length human SERCA3 promoter was 50% lower in biotin-supplemented cells compared to biotin-deficient cells. Biotin-dependent repressors bind to elements located 731 to 1312 bp upstream from the transcription start site in the SERCA3 gene. The following suggest that low expression of SERCA3 in biotin-supplemented cells impaired folding of secretory proteins in the ER, triggering unfolded protein response: (i) sequestration of Ca2+ in the ER decreased by 14 to 24% in response to biotin supplementation; (ii) secretion of interleukin-2 into the extracellular space decreased by 75% in response to biotin supplementation; (iii) the nuclear abundance of stress-induced transcription factors increased in response to biotin supplementation; and (iv) the abundance of stress-related proteins such ubiquitin activating enzyme 1, growth arrest and DNA damage 153 gene, X-box binding protein 1 and phosphorylated eukaryotic translation initiation factor 2alpha increased in response to biotin supplementation. Collectively, this study suggests that supplements containing pharmacological doses of biotin may cause cell stress by impairing protein folding in the ER. Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have

Pharmacodynamics

Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or "cradle cap". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes.

Mechanism of action

Vitamin K is a cofactor of gamma-carboxylase. Gamma carboxylase attaches carboxylic acid functional groups to glutamate, allowing precursors of factors II, VII, IX, and X to bind calcium ions. Binding of calcium ions converts these clotting factors to their active form, which are then secreted from hepatocytes into the blood, restoring normal clotting function. Vitamin K may also carboxylate matrix proteins in chondrocytes, inhibiting calcification of joints, and may increase type II collagen. The role of vitamin K in osteroarthritis, bone density, and vascular calcification is currently under investigation. Vit k is necessary for formation of prothrombinogen & other blood clotting factors in liver. During clotting, circulating prothrombin is required for production of thrombin; in turn, thrombin converts fibrinogen to fibrin, network of which constitutes clot. /vit k/ In normal animals and man, phyltonadione ... /is/ virtually devoid of pharmacodynamic activity. In Animals and man deficient in vitamin k, the pharmacological action of vitamin k is identical to its normal physiological function, that is, to promote hepatic biosynthesis of prothrombin (factor ii), proconvertin (factor vii), plasma thromboplastin component (ptc, christmas factor, factor ix), and Stuart factor (factor x). On the basis of studies of microsomal metabolism in vitro and studies in rats and mice in vivo, /it was suggested/ that vitamin K may be mutagenic by affecting the mixed-function oxidase system which metabolizes benzo(a)pyrene. Phylloquinone at a high concentration (200 umol/l) inhibited the conversion of benzo(a)pyrene to its more polar metabolites, ... . Paradoxically, at a lower concentration of phylloquinone (25 umol/l), ... the metabolism of benzo(a)pyrene was increased. In this system, therefore, .... phylloquinone could either potentiate or inhibit it, depending on the concentration. This overall weaker inhibitory effect of phylloquinone could be due to the low solubility of this lipophilic compound, but it is difficult to explain the mechanism of the enhanced metabolism of benzo(a)pyrene at lower concentrations of phylloquinone.

Pharmacodynamics

Phylloquinone is a vitamin K indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K. It has a long duration of action as vitamin K is cycled in the body, and a wide therapeutic index as large doses can be tolerated. Patients should have their prothrombin time monitored during therapy and healthcare professionals should be aware of the increased risk of hypersensitivity reactions with parenteral administration.

Mechanism of action

It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions. Metabolic control analysis predicts that stimulators of transketolase enzyme synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation. Metabolic control analysis also predicts that transketolase inhibitor drugs will have the opposite effect on tumor cells. This may have important implications in the nutrition and future treatment of patients with cancer.

Pharmacodynamics

Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.

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

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase. Folic acid, after conversion to tetrahydrofolic acid, is necessary for normal erythropoiesis, synthesis of purine and thymidylates, metabolism of amino acids such as glycine and methionine, and the metabolism of histidine. The principal biochemical function of folates is the mediation of one-carbon transfer reactions. 5-Methyltetrahydrofolate donates a methyl group to homocystine, in the conversion of homocystine to L-methionine. ... 5,10-Methyltetrahydrofolate is regenerated from tetrahydrofolate via the enzyme serine hydroxymethyltransferase, a reaction, which in addition to producing 5,10-methyltetrahydrofolate, yields glycine. ... 5,10-methyltetrahydrofolate, supplies the one carbon group for the methylation of deoxyuridylic acid to form the DNA precursor thymidylic acid. This reaction is catalyzed by thymidylate synthase and the folate product of the reaction is dihydrofolate. Dihydrofolate is converted to tetrahydrofolate via the enzyme dihydrofolate reductase ...

Pharmacodynamics

Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as [DB00563] as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.

Mechanism of action

... Excessive palmitoylcarnitine formation and exhausted L-carnitine stores leading to energy depletion, attenuated acetylcholine synthesis and oxidative stress to be main mechanisms behind PA-induced neuronal loss.High PA exposure is suggested to be a factor in causing diabetic neuropathy and gastrointestinal dysregulation. ... First phase insulin release response was lost in these islets. FFAs slightly increased the insulin output of normal fresh pancreas beta-cells. However, chronic exposure to FFAs resulted in loss of first phase insulin release and blunted insulin secretion response to various levels of D-glucose stimulation.

Pharmacodynamics

Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation

Mechanism of action

Panthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol, the active form of panthenol, is enzymatically cleaved to form pantothenic acid (Vitamin B5), which is an essential component of Coenzyme A that acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium. Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties.

Pharmacodynamics

Pantothenic acid is a precursor of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions involving transfer of acetyl groups. The final step in the synthesis of acetylcholine consists of the choline acetylase transfer of acetyl group from acetylcoenzyme A to choline. Acetylcholine is the neurohumoral transmitter in the parasympathetic system and as such maintains the normal functions of the intestine. Decrease in acetylcholine content would result in decreased peristalsis and in extreme cases adynamic ileus.

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.