AMINOVITALYTE WATER SOLUBLE POWDER (Each 1000gram contains: Vitamin A 13,500,000iu/ Vitamin D3 4,150,000iu/ Vitamin E 3750mg/ Vitamin K 4500mg/ Vitamin B2 4,500mg/ Vitamin B6 3000mg/ Vitamin B12 11,500mcg/ Vitamin C 5,000mg/ Biotin 50mcg/ Folic Acid 1,000mg/ Niacin 16,750mg/ Citric Acid 10,000mg/ Glutamic Acid 1660mg/ Proline 4,800mg/ Threonine 52,500mg/ Glycine 3820mg/ L-Lysine 16,000mg/ DL-Methionine 12,000mg/ D-Calcium Pantothenate 8000mg/ Dicalcium Phosphate 10,000mg/ Magnesium Sulphate 4000mg/ Manganese Sulphate 4000mg/ Copper Sulphate 7500mg/ Zinc Sulphate 1500mg/ Iron Sulphate 5000mg/ Sodium Chloride 50,000mg/ Potassium Chloride 88,000mg/ Sodium Selenite 50mg/ Probiotics(Lactic Acid Baccillus ) 5,000,000CFU)

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

• Bladder irrigation during urological surgery
• Irrigation for transurethral resection of the prostate gland
• Irrigation for bladder tumors

Dosage

Children: Refer to the BNF for Children for pediatric dosing guidelines.

Adults: Refer to the product literature for specific dosing information.

Mechanism of action

Glycine binds to strychnine-sensitive and strychnine-insensitive glycine receptors in the central nervous system. The strychnine-sensitive receptor is a chloride channel that enhances inhibitory neurotransmission. This action may contribute to glycine's potential antispastic effects. Additionally, glycine potentiates NMDA receptor-mediated neurotransmission, which may have implications in managing certain neurological conditions, such as neuroleptic-resistant negative symptoms in schizophrenia.

Pharmacodynamics

Glycine plays a crucial role in various biological functions, including energy metabolism and immune response. It is involved in hormone synthesis and helps in modulating neurotransmitter release, particularly in inhibitory pathways. Glycine's ability to enhance chloride conductance in neurons contributes to its antispastic properties and its potential to mitigate oxidative stress in immune responses.

Pharmacokinetics

Glycine is absorbed readily in the gastrointestinal tract and is utilized by the body for protein synthesis and other metabolic functions. The distribution of glycine in the body is widespread, as it is present in various tissues. Glycine is metabolized in the liver and other tissues, with excretion primarily occurring via the kidneys. The pharmacokinetics of glycine can be influenced by factors such as age, renal function, and overall health status.

Adverse effects

• Fluid overload
• Electrolyte imbalance
• Nausea
• Vomiting
• Headache
• Hypotension

Precautions

• Monitor for signs of fluid overload during irrigation
• Use caution in patients with pre-existing electrolyte imbalances
• Careful consideration in patients with renal impairment

Pregnancy

Glycine is generally considered safe for use during pregnancy when used as an irrigation solution, but risks should be discussed with a healthcare provider.

Breast-feeding

Glycine is likely safe during breastfeeding, but limited data is available. Consultation with a healthcare professional is advisable.

Storage

Store in a cool, dry place. Protect from light. Do not freeze.

Formulations

• Glycine 1.5% irrigation solution 3 litre Easyflow bags
• Glycine 1.5% irrigation solution 1 litre Flowfusor bottles
• Glycine 1.5% irrigation solution 1 litre Easyflow bags
• Glycine 1.5% irrigation solution 2 litre Flowfusor bottles

Dosage

Children: Refer to clinical guidelines or established pharmacology for dosing information.

Adults: Refer to clinical guidelines or established pharmacology for dosing information.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. The drug may pass into breast milk and affect the nursing infant.

Storage

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

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

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

Indications

• Copper deficiency
• Occipital Horn Syndrome
• Menke's disease
• Contraception (via copper IUD)

Dosage

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

Adults: Refer to the relevant clinical guidelines and BNF for specific dosing information.

Mechanism of action

Copper is absorbed from the gastrointestinal tract via high affinity copper uptake proteins and low affinity copper uptake proteins, likely being reduced to the Cu1+ form prior to transport. Inside enterocytes, it binds to the copper transport protein ATOX1, which facilitates its transport to copper transporting ATPase-1 on the Golgi membrane for incorporation into the Golgi apparatus. Once in systemic circulation, copper binds primarily to ceruloplasmin, albumin, and alpha 2-macroglobulin. It acts as a cofactor in a variety of oxidase enzymes and also influences sperm motility when released from copper IUDs, contributing to its contraceptive effect.

Pharmacodynamics

Copper is essential for the activity of many enzymes and plays a vital role in processes such as iron metabolism, neurotransmitter synthesis, and antioxidant defense. Copper ions, particularly when released from intrauterine devices, have been shown to decrease sperm viability, thereby impacting fertility.

Pharmacokinetics

Copper is absorbed from the gut and is predominantly transported in the plasma bound to proteins such as ceruloplasmin and albumin. The absorption efficiency can vary; however, a significant portion of dietary copper is usually absorbed. The body regulates copper levels through hepatic excretion and storage mechanisms, ensuring homeostasis. Excess copper can lead to toxicity, while deficiency results in various health issues.

Pregnancy

Copper is considered essential during pregnancy, but excessive intake should be avoided due to potential toxicity.

Breast-feeding

Copper is excreted in breast milk, and adequate maternal intake is important for infant development.

Storage

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

Indications

• Calcium deficiency
• Osteoporosis prevention
• Osteomalacia
• Rickets
• Dietary supplementation in individuals with increased calcium and phosphorus requirements

Dosage

Children: Refer to established guidelines for specific dosing based on clinical indications and individual patient needs.

Adults: Refer to established guidelines for specific dosing based on clinical indications and individual patient needs.

Mechanism of action

Dicalcium phosphate dissociates in the gastrointestinal tract to release calcium and phosphate ions. Calcium plays a vital role in various physiological processes, including muscle contraction, neurotransmitter release, and blood coagulation. The phosphate ions are essential for energy metabolism and are integral to the formation of ATP (adenosine triphosphate), nucleic acids, and cellular membranes. The availability of these ions supports bone mineralization and overall skeletal integrity.

Pharmacodynamics

The pharmacodynamics of dicalcium phosphate involves its role in maintaining calcium and phosphate homeostasis in the body. Adequate levels of calcium are critical for normal bone metabolism, while phosphate is necessary for the formation of hydroxyapatite in bone tissue. The balance of these minerals is regulated by hormones such as parathyroid hormone and calcitriol, which modulate their absorption in the intestines and reabsorption in the kidneys. Supplementation with dicalcium phosphate can help alleviate deficiencies and support bone health.

Pharmacokinetics

Dicalcium phosphate is absorbed in the gastrointestinal tract, with varying absorption rates depending on the presence of other dietary components. Calcium absorption occurs primarily in the small intestine, while phosphate absorption can occur throughout the gastrointestinal tract. After absorption, calcium is distributed to bones, teeth, and soft tissues, while excess calcium is excreted through urine. The pharmacokinetics may be influenced by factors such as age, dietary habits, and the presence of gastrointestinal disorders.

Adverse effects

• Gastrointestinal disturbances (nausea, constipation)
• Hypercalcemia
• Kidney stones
• Fatigue
• Muscle weakness

Interactions

• May interact with calcium channel blockers
• Increased risk of hypercalcemia with thiazide diuretics
• May affect the absorption of certain antibiotics (e.g., tetracyclines)

Precautions

• Use with caution in patients with renal impairment
• Monitor calcium levels in patients receiving high doses
• Consider potential interactions with other medications

Pregnancy

Dicalcium is generally considered safe in pregnancy when used as directed, but high doses should be avoided.

Breast-feeding

Calcium is an essential nutrient during breastfeeding, but excessive supplementation should be approached with caution.

Storage

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

Formulations

• Tablets
• Powders
• Chewable tablets

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

Indications

• Nutritional supplementation
• Support in neurological disorders
• Enhancement of cognitive function

Dosage

Children: Refer to established guidelines for specific dosing recommendations.

Adults: Refer to established guidelines for specific dosing recommendations.

Mechanism of action

Glutamic acid primarily functions as an excitatory neurotransmitter by binding to and activating glutamate receptors, which include NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), and kainate receptors. This binding leads to an influx of calcium ions and sodium ions into neurons, resulting in depolarization and the propagation of excitatory signals across synapses. It is also involved in the synthesis of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.

Pharmacodynamics

Glutamic acid has a significant role in neurotransmission, influencing synaptic plasticity, which is essential for learning and memory. It is involved in various physiological processes, including neuronal development and the regulation of synaptic strength. Dysregulation of glutamate signaling is implicated in several neurological disorders, including epilepsy, Alzheimer's disease, and schizophrenia.

Pharmacokinetics

Glutamic acid is rapidly absorbed from the gastrointestinal tract. It is found in high concentrations in the brain and is distributed widely in tissues. The metabolism of glutamate occurs primarily in the brain and liver, where it can be converted to other amino acids or used in the Krebs cycle for energy production. Glutamate is predominantly excreted as ammonia and urea. The half-life of glutamate in the body is relatively short due to its rapid utilization and metabolism.

Contra-indications

• Hypersensitivity to glutamic acid or any of its components
• Severe liver disease

Adverse effects

• Headache
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hypersensitivity reactions such as rash or itching

Interactions

• May interact with medications that alter amino acid metabolism
• Potential interactions with drugs affecting neurotransmitter levels

Precautions

• Use with caution in patients with renal impairment
• Monitor patients with a history of seizures or neurological disorders

Pregnancy

Glutamic acid is generally considered safe in pregnancy, but should be used under medical supervision.

Breast-feeding

It is likely safe during breastfeeding, but caution is advised.

Storage

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

Formulations

• Oral tablets
• Powder for oral solution
• Injectable form

Indications

• Manganese deficiency
• Bone health and development
• Antioxidant support
• Enzyme cofactor in metabolic processes

Dosage

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

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

Mechanism of action

Manganese serves as a cofactor for several enzymes, including manganese superoxide dismutase (MnSOD), which protects cells from oxidative stress by catalyzing the dismutation of superoxide radicals into oxygen and hydrogen peroxide. It also participates in the activation of enzymes involved in carbohydrate, fat, and protein metabolism.

Pharmacodynamics

Manganese plays a role in various biochemical pathways, particularly in the metabolism of amino acids, cholesterol, glucose, and carbohydrates. It is crucial for bone formation and the maintenance of cartilage. Manganese also aids in the synthesis of glycosyltransferases, which are important for the formation of glycoproteins and proteoglycans.

Pharmacokinetics

Manganese is absorbed primarily in the small intestine, with absorption efficiency influenced by dietary factors and the presence of competing minerals. It is transported in the bloodstream bound to proteins such as alpha-2-macroglobulin and transferrin. Manganese is stored in the liver, pancreas, and bones, and is excreted primarily through bile and to a lesser extent in urine. Its half-life in the human body is not well defined due to its trace nature and variable absorption.

Pregnancy

Manganese is classified as a dietary mineral that is essential for human health, but excessive intake should be avoided during pregnancy as it may affect fetal development.

Breast-feeding

Manganese is present in breast milk, and normal dietary intake is considered safe during breastfeeding. However, excessive supplementation should be avoided.

Storage

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

Indications

• Vitamin B3 deficiency
• Hyperlipidemia
• Dyslipidemia

Mechanism of action

Niacin decreases lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver and inhibiting lipolysis in adipose tissue. It inhibits hepatocyte diacylglycerol acyltransferase-2, preventing the final step of triglyceride synthesis, leading to reduced VLDL production. Additionally, niacin inhibits HDL catabolism receptors, increasing HDL levels and half-life. Acute effects include inhibition of nonesterified fatty acid release from adipocytes and stimulation of prostaglandin release from skin Langerhans cells, although these acute effects diminish over time.

Pharmacodynamics

Niacin is used therapeutically to treat vitamin deficiencies and to manage conditions like hyperlipidemia and dyslipidemia. It effectively reduces levels of VLDL and LDL while increasing HDL levels. Niacin has a wide therapeutic window, with typical oral doses ranging from 500 mg to 2000 mg. Caution is advised in patients with diabetes, renal failure, uncontrolled hypothyroidism, and in elderly patients, particularly when combined with simvastatin or lovastatin, due to an increased risk of myopathy and rhabdomyolysis.

Pharmacokinetics

Niacin is absorbed from the gastrointestinal tract and undergoes hepatic metabolism. It is excreted primarily in the urine. The pharmacokinetics can be affected by factors such as age, renal function, and concomitant medications. Peak plasma concentrations are typically reached within 30 minutes to 2 hours after oral administration, depending on the formulation used.

Contra-indications

• Hypersensitivity to niacin or any of its components
• Active liver disease
• Peptic ulcer disease

Adverse effects

• Flushing
• Itching
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hepatotoxicity
• Hyperglycemia
• Gout exacerbation

Interactions

• Increased risk of myopathy and rhabdomyolysis with statins such as simvastatin or lovastatin
• May enhance the effects of antihypertensive medications
• Potential interaction with anticoagulants

Precautions

• Caution in patients with diabetes due to potential for hyperglycemia
• Monitor liver function tests periodically during prolonged therapy
• Use with caution in patients with renal impairment
• Elderly patients may be more susceptible to adverse effects

Pregnancy

Niacin should only be used during pregnancy if clearly needed and the benefits outweigh the risks. Consult with a healthcare provider for individual assessment.

Breast-feeding

Niacin is excreted in breast milk. Caution is advised when administering to nursing mothers, and a decision should be made whether to discontinue breastfeeding or the drug.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Immediate-release tablets
• Extended-release tablets
• Sustained-release tablets

Indications

• Pantothenate deficiency
• Support in energy metabolism
• Adjuvant therapy in chronic conditions requiring enhanced energy production

Dosage

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

Adults: Refer to the BNF for specific dosing information, generally 5-10 mg daily for adults.

Mechanism of action

Pantothenate functions primarily as a precursor to coenzyme A (CoA), which is vital for various biochemical reactions in the body. CoA is involved in the metabolism of fatty acids, the synthesis of cholesterol and steroid hormones, and the acetylation of various substrates, which is crucial for energy production and metabolic processes.

Pharmacodynamics

Pantothenate plays a significant role in energy metabolism, cellular respiration, and the biosynthesis of fatty acids. It facilitates the transfer of acyl groups, which is critical for the metabolism of carbohydrates and fats, thereby influencing the overall energy production in cells. Adequate levels of pantothenate are necessary for maintaining metabolic homeostasis and supporting growth and development.

Pharmacokinetics

Pantothenate is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 70%. Once absorbed, it is widely distributed throughout the body, particularly in the liver, adrenal glands, and kidneys. The vitamin is metabolized primarily in the liver, where it is converted to coenzyme A. Excess pantothenate is excreted in the urine as pantothenic acid and its metabolites. The half-life of pantothenate in the body is not well-defined but is generally considered to be relatively short due to its water-soluble nature.

Pregnancy

Pantothenic acid (Vitamin B5) is generally regarded as safe during pregnancy. It is important to maintain adequate levels for fetal development.

Breast-feeding

Pantothenic acid is excreted in breast milk in small amounts. Adequate intake is important for breastfeeding mothers, but supplementation is typically not necessary.

Storage

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

Formulations

• Pantothenate tablets
• Pantothenic acid capsules
• Pantothenate injections

Indications

• Antibiotic-associated diarrhea
• Irritable bowel syndrome (IBS)
• Inflammatory bowel disease (IBD)
• Acute gastroenteritis
• Lactose intolerance
• Prevention of infections in immunocompromised patients
• Support for gut health during and after antibiotic treatment

Dosage

Children: Refer to specific product guidelines as dosing can vary

Adults: Refer to specific product guidelines as dosing can vary by strain and indication.

Mechanism of action

Probiotics exert their effects through various mechanisms including competition with pathogenic microorganisms for adhesion sites on the intestinal mucosa, production of antimicrobial substances such as bacteriocins, modulation of the immune response, and enhancement of the intestinal barrier function. They may also influence the gut-brain axis and metabolic pathways by producing short-chain fatty acids (SCFAs) from dietary fibers, which can provide energy to colonic cells and modulate inflammation.

Pharmacodynamics

Probiotics can enhance the gut microbiota diversity and functional capacity, leading to improved gut health and overall well-being. They may reduce the incidence and duration of gastrointestinal infections, alleviate symptoms of irritable bowel syndrome (IBS), and prevent antibiotic-associated diarrhea. Their immunomodulatory effects can help in managing allergic conditions and may support the body’s response to infections.

Pharmacokinetics

Probiotics are generally administered orally, where they travel through the gastrointestinal tract. Their survival and colonization depend on factors such as the strain, the pH of the environment, and the presence of prebiotics. While some strains can transiently colonize the gut, others may adhere more permanently. The bioavailability of probiotics can be influenced by the formulation, with enteric-coated capsules designed to protect them from gastric acid. The effects of probiotics can be observed within days to weeks, depending on the condition being treated.

Adverse effects

• Gastrointestinal discomfort
• Flatulence
• Bloating
• Diarrhea
• Infections in immunocompromised patients

Precautions

• Use cautiously in patients with underlying health conditions, particularly those with weakened immune systems
• Monitor for gastrointestinal symptoms
• Consult healthcare professional before use in children or during pregnancy

Pregnancy

Generally considered safe, but consult a healthcare professional before use.

Breast-feeding

Typically safe, but check with a healthcare provider.

Storage

Store in a cool, dry place. Some formulations may require refrigeration.

Formulations

• Capsules
• Tablets
• Powders
• Liquid formulations
• Probiotic-enriched foods (e.g., yogurt)

Indications

• Support for connective tissue health
• Muscle repair
• Joint and tendon function
• Skin health maintenance
• Cardiovascular support

Dosage

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

Adults: Refer to BNF for appropriate dosing guidance.

Mechanism of action

Proline is glycogenic, and in the kidney, it is oxidized to form L-Glutamic acid via L-Proline oxidase. L-Glutamic acid and L-Ornithine can be converted back to L-Proline through L-Glutamic acid-gamma-semialdehyde. This metabolic pathway underscores its role in amino acid metabolism and collagen synthesis.

Pharmacodynamics

L-Proline is a major amino acid in cartilage, playing a significant role in maintaining skin elasticity and facilitating the repair of muscle and connective tissue damage. It is essential for the immune system and contributes to the structural functions of joints and tendons. Furthermore, L-Proline supports heart muscle function, thereby promoting cardiovascular health.

Pharmacokinetics

L-Proline is metabolized primarily in the liver and kidneys. Its absorption occurs in the gastrointestinal tract following dietary intake. Once absorbed, it participates in various metabolic pathways, including proline metabolism and tRNA charging, which are crucial for protein synthesis.

Pregnancy

Safety during pregnancy has not been established. Consult a healthcare provider before use.

Breast-feeding

Safety during breastfeeding has not been established. Consult a healthcare provider before use.

Storage

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

Formulations

• Powder
• Capsules
• Tablets

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

• Selenium deficiency
• Antioxidant therapy
• Support in thyroid function
• Potential adjunctive treatment in cancer therapy

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Selenite acts as a source of selenium, which is incorporated into selenoproteins. These proteins play essential roles in antioxidant defense, thyroid hormone metabolism, and immune function. The selenium from selenite is metabolized to selenophosphate, which is a precursor for the synthesis of selenoamino acids and subsequently selenoproteins.

Pharmacodynamics

Selenite exhibits antioxidant properties by enhancing the activity of antioxidant enzymes, such as glutathione peroxidase. This helps to reduce oxidative stress in the body. The effects of selenite can vary depending on the dose and duration of exposure, with low doses being beneficial and high doses potentially leading to toxicity.

Pharmacokinetics

Selenite is absorbed in the gastrointestinal tract and is distributed throughout the body, with a preference for high accumulation in the liver, kidney, and muscle tissues. The elimination half-life of selenium varies but is generally a few days. Selenium is primarily excreted through urine, and its metabolism involves conversion to various seleno compounds.

Formulations

• Sodium selenite

Indications

• Essential amino acid supplementation
• Support for liver function
• Improvement of protein synthesis
• Support in the formation of collagen and elastin
• Aid in digestive health

Dosage

Children: Refer to BNF for Children for appropriate dosage guidelines.

Adults: Refer to BNF for appropriate dosage guidelines.

Mechanism of action

L-Threonine acts as a precursor to the amino acids glycine and serine. It aids in protein synthesis by binding with transfer RNA (tRNA) in the cytoplasm, facilitating the translation of messenger RNA (mRNA) into specific proteins. Threonine's role in lipotropic function helps control fat build-up in the liver and enhances nutrient absorption.

Pharmacodynamics

L-Threonine is essential for maintaining proper protein balance in the body. It supports the synthesis of critical structural proteins and plays a role in metabolic functions related to liver health. Threonine also aids in the formation of collagen and elastin, which are vital for skin and connective tissue integrity.

Pharmacokinetics

Threonine is absorbed in the intestines and utilized by various tissues throughout the body. As an essential amino acid, it cannot be synthesized by the body and must be obtained from dietary sources. Once absorbed, threonine is incorporated into proteins or converted into other metabolites as needed for various physiological functions.

Pregnancy

Threonine is generally considered safe during pregnancy as it is an essential amino acid required for fetal development.

Breast-feeding

Threonine is also considered safe during breastfeeding, as it is essential for protein synthesis and overall growth in infants.

Storage

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

Indications

• Prevention of vitamin E deficiency
• Antioxidant therapy
• Support in conditions related to oxidative stress

Dosage

Children: Refer to BNF for Children for specific dosage guidelines.

Adults: Refer to BNF for specific dosage guidelines.

Mechanism of action

Tocopherol acts as a radical scavenger, primarily functioning as an antioxidant for lipid bilayers. It donates hydrogen atoms to free radicals, trapping them and preventing cellular damage. Its effectiveness is influenced by its location within the membrane and its interaction with cytosolic reductants like ascorbate. Tocopherol can trap multiple radicals, including alkyl and peroxy radicals.

Pharmacodynamics

The antioxidant properties of tocopherol lead to significant pharmacodynamic effects, including the inhibition of cell death through modulation of protein kinase C (PKC). Tocopherol also exhibits anti-inflammatory effects, which can be attributed to its influence on cytokines, prostaglandins, prostanoids, and thromboxanes. These interactions may contribute to its protective effects in various pathological conditions.

Pharmacokinetics

Tocopherol is absorbed in the intestines and its bioavailability can be influenced by dietary fat intake. It is transported in the plasma primarily bound to lipoproteins. Tocopherol is stored in adipose tissue and the liver, and its elimination occurs through bile and urine. The half-life of tocopherol can vary depending on the individual's nutritional status and other factors.

Pregnancy

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

Breast-feeding

Tocopherol is excreted in breast milk, and while it is considered safe, a healthcare provider should be consulted for specific recommendations.

Storage

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

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

In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia. Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS. HYPERPOLARIZATION OF MOTONEURONS PRODUCED BY IONTOPHORETIC APPLICATION OF GLYCINE IS RELATIVELY TRANSIENT BUT APPROACHES THE EQUILIBRIUM POTENTIAL FOR THE INDIRECTLY ACTIVATED INHIBITORY POSTSYNAPTIC POTENTIAL...TESTS WITH GABA... INDICATE SIMILAR ELECTROPHYSIOLOGICAL EFFECTS & SIMILAR INCR IN CL- CONDUCTANCE. MAJOR EVIDENCE THAT FAVORS GLYCINE AS MEDIATOR OF INTRASPINAL POSTSYNAPTIC INHIBITION IS THE SELECTIVE ANTAGONISM OF ITS EFFECTS BY STRYCHNINE. ... GLYCINE ALSO APPEARS TO BE MOST LIKELY TRANSMITTER FOR INHIBITORY INTERNEURONS IN RETICULAR FORMATION BUT NOT IN CUNEATE NUCLEUS.

Pharmacodynamics

Helps trigger the release of oxygen to the energy requiring cell-making process; Important in the manufacturing of hormones responsible for a strong immune system.

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

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2. It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%). Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor. It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor. Copper appears to reduce the viabilty and motility of spermatozoa. This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect. The exact mechanism of copper's effect on sperm are unknown. The reason for the less severe reaction when the foreign body is at a distance from the retina has been proposed to be ... that near the retina & its blood vessels there is greater oxygen tension than at a distance, which causes metallic copper to oxidize to toxic copper compounds more rapidly close to or in contact with the retina than at a distance. Furthermore, the abscess formation that is characteristic of copper undergoing oxidation close to the retina & choroiod can be attributed to attraction of polymorphonuclear leukocytes from these nearby vascular tissues, which become heavily infiltrated. Liquefaction & disorganization of the vitreous body has been explained on the basis of copper catalysis of oxidation of ascorbic acid, leading to depolymerization of the hyaluronic acid of the vitreous humor. Changes in protein & hexosamine content have also been related to decrease in viscosity of the vitreous humor. Increased content of amino acids in the vitreous humor has been consistent with proteolysis of the vitreous body, but decreased concentration in the aqueous humor has suggested suppression of secretion of amino acids by the ciliary body under the influence of copper.

Pharmacodynamics

Copper is incorporated into many enzymes throughout the body as an essential part of their function. Copper ions are known to reduce fertility when released from copper-containing IUDs.

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

Niacin performs a number of functions in the body and so has many mechanisms, not all of which have been fully described. Niacin can decrease lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver, which degrades apo B, or by modulating lipolysis in adipose tissue. Niacin inhibits hepatocyte diacylglycerol acyltransferase-2. This action prevents the final step of triglyceride synthesis in hepatocytes, limiting available triglycerides for very low density lipoproteins (VLDL). This activity also leads to intracellular degradation of apo B and decreased production of low density lipoproteins, the catabolic product of VLDL. Niacin also inhibits a high density lipoprotein (HDL) catabolism receptor, which increases the levels and half life of HDL. Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. /The study objective was/ to determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/-) (niacin receptor(-/-)) mice. Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/-) mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARgamma C/EBPalpha or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lalpha, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1beta in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expressio

Pharmacodynamics

Niacin is a B vitamin used to treat vitamin deficiencies as well as hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarctions. Niacin acts to decrease levels of very low density lipoproteins and low density lipoproteins, while increasing levels of high density lipoproteins. Niacin has a wide therapeutic window with usual oral doses between 500mg and 2000mg. Patients with diabetes, renal failure, uncontrolled hypothyroidism, and elderly patients taking niacin with simvastatin or lovastatin are at increased risk of myopathy and rhabdomyolysis.

Mechanism of action

Glycogenic, by L-Proline oxidase in the kidney, it is ring-opened and is oxidized to form L-Glutamic acid. L-Ornithine and L-Glutamic acid are converted to L-Proline via L-Glutamic acid-gamma-semialdehyde. It is contained abundantly in collagen, and is intimately involved in the function of arthrosis and chordae.

Pharmacodynamics

L-Proline is a major amino acid found in cartilage and is important for maintaining youthful skin as well as repair of muscle, connective tissue and skin damage. It is also essential for the immune system, and for necessary balance of this formula. It is an essential component of collagen and is important for proper functioning of joints and tendons. L-Proline is extremely important for the proper functioning of joints and tendons. Helps maintain and strengthen heart muscles.

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.

Mechanism of action

L-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present. Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Protein synthesis/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Protein degradation/

Pharmacodynamics

L-Threonine is an essential amino acid that helps to maintain the proper protein balance in the body. It is important for the formation of collagen, elastin, and tooth enamel, and aids liver and lipotropic function when combined with aspartic acid and methionine.

Mechanism of action

Tocopherol acts as a radical scavenger. It mainly acts as an antioxidant for lipid bilayers. Tocopherol's functions depend on the H-atom donating ability, location, and movement within the membrane, as well as the efficiency in the radical recycling by some cytosolic reductants such as ascorbate. Tocopherol actions are related to the trap of radicals, and it has been shown that even in the absence of substituents in the ortho-positions, tocopherol can trap more than two radicals. The type of radicals available for tocopherol are alkyl and peroxy.

Pharmacodynamics

The antioxidant effects of tocopherol can be translated into different changes at the pharmacodynamic level. In vitro studies have shown that this antioxidant activity can produce modification in protein kinase C (PKC) which will later be translated into an inhibition of cell death. Some other derivate effects are the anti-inflammatory properties of tocopherol which can be related to the modulation of cytokines or prostaglandins, prostanoids and thromboxanes.