Gromin

Indications

• Vitamin C deficiency
• Scurvy
• Adjunct therapy in iron overload conditions

Dosage

Children: Child 1 month–3 years: 125–250 mg daily in 1–2 divided doses; Child 4–11 years: 250–500 mg daily in 1–2 divided doses; Child 12–17 years: 0.5–1 g daily in 1–2 divided doses.

Adults: 500 mg daily, taken in 1-2 divided doses, depending on the clinical condition and dietary needs.

Mechanism of action

Ascorbic acid functions primarily as a reducing agent, facilitating enzymatic reactions in the body, including the hydroxylation of proline and lysine in collagen synthesis. It also plays a role in the absorption of iron from the gastrointestinal tract and enhances the immune response.

Pharmacodynamics

Ascorbic acid is crucial for the maintenance of connective tissue and is involved in the metabolism of several amino acids. Its antioxidant properties help to mitigate oxidative stress and may play a role in reducing the risk of chronic diseases.

Pharmacokinetics

Ascorbic acid is absorbed in the intestines and is widely distributed throughout the body. The renal clearance of ascorbic acid is dose-dependent, with higher doses leading to increased excretion. The half-life varies but is generally around 15 to 30 minutes in healthy individuals, with tissue saturation levels influencing its retention.

Contra-indications

• Hypercalcaemia
• Hyperoxaluria
• Patients with cardiac dysfunction

Adverse effects

• Abdominal pain
• Headache
• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Weight loss
• Polyuria
• Sweating
• Thirst
• Vertigo

Interactions

• Increases risk of cardiovascular adverse effects with iron chelators
• Increases risk of cardiovascular adverse effects with deferiprone
• Increases risk of cardiovascular adverse effects with desferrioxamine

Precautions

• Use with caution in patients with iron overload
• Monitor for symptoms of overdose

Pregnancy

High doses teratogenic in animals but therapeutic doses unlikely to be harmful.

Storage

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

Formulations

• Ascorbic acid 50 mg tablets
• Ascorbic acid 100 mg tablets
• Ascorbic acid 200 mg tablets
• Ascorbic acid 250 mg tablets
• Ascorbic acid 500 mg capsules

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 D deficiency
• Rickets
• Osteomalacia
• Osteoporosis
• Hypoparathyroidism

Dosage

Adults: The usual adult dose for vitamin D deficiency is 800 to 2000 IU daily, depending on the severity of deficiency and clinical condition. Higher doses may be used under medical supervision.

Mechanism of action

Cholecalciferol is converted to its active forms, 25-hydroxyvitamin D in the liver and 1,25-dihydroxyvitamin D in the kidneys. These metabolites enhance the intestinal absorption of calcium and phosphorus, increase serum calcium levels, and mobilize these minerals from bone. This process is regulated by parathyroid hormone, which influences calcium and phosphate metabolism, particularly in the kidneys.

Pharmacodynamics

The pharmacodynamics of cholecalciferol involve its conversion to active metabolites that play a significant role in calcium and phosphorus homeostasis. The metabolites facilitate intestinal absorption of these minerals, promote bone mineralization, and influence renal reabsorption. The onset of action occurs within 10 to 24 hours following administration, as metabolic activation is required for its biological effects.

Pharmacokinetics

Cholecalciferol is absorbed in the gastrointestinal tract, and its absorption is enhanced by the presence of dietary fats. It is transported in the bloodstream bound to vitamin D-binding protein. Once in the liver, it undergoes hydroxylation to form 25-hydroxyvitamin D, which is further converted in the kidneys to the active form, 1,25-dihydroxyvitamin D. The elimination half-life of cholecalciferol varies, typically spanning several days, and it is primarily excreted in bile and urine.

Adverse effects

• Hypercalcemia
• Hypercalciuria
• Nausea
• Vomiting
• Constipation
• Weakness
• Fatigue

Interactions

• May enhance the effects of thiazide diuretics, leading to increased risk of hypercalcemia
• Anticonvulsants may increase metabolism of vitamin D, leading to reduced effectiveness
• Cholestyramine may reduce absorption of vitamin D

Precautions

• Monitor serum calcium levels in patients with renal impairment
• Caution in patients with a history of hypercalcemia or hyperparathyroidism
• Use with caution in patients taking other medications that affect calcium metabolism

Pregnancy

Cholecalciferol can be used during pregnancy if indicated, as vitamin D is essential for fetal bone development.

Breast-feeding

Cholecalciferol is excreted in breast milk, but is generally considered safe during breastfeeding.

Storage

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

Formulations

• Capsules
• Tablets
• Liquid formulations

Indications

• Wound healing
• Skin moisturizing
• Epithelial protection
• Treatment of skin irritations
• Topical anti-inflammatory treatment

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on age and condition.

Adults: Topical application as needed, typically applied to the affected area 1 to 3 times daily.

Mechanism of action

Dexpanthenol is enzymatically converted to pantothenic acid, a precursor of coenzyme A. This coenzyme acts as a cofactor in numerous enzymatic reactions critical for protein metabolism, particularly in epithelial cells. Topically, dexpanthenol enhances fibroblast proliferation and accelerates re-epithelialization in wound healing. It also functions as a moisturizer and has anti-inflammatory properties. Additionally, it increases the availability of coenzyme A for synthesizing acetylcholine, which is essential for maintaining intestinal tone and peristalsis.

Pharmacodynamics

Dexpanthenol, through its active form pantothenic acid, contributes to various biochemical pathways, particularly those involving the synthesis of coenzyme A. This coenzyme facilitates the transfer of acetyl groups necessary for the synthesis of acetylcholine, a neurotransmitter that regulates parasympathetic nervous system functions, including gastrointestinal motility. Enhanced levels of acetylcholine promote normal intestinal functions, while a deficiency may lead to decreased peristalsis.

Pharmacokinetics

Dexpanthenol is readily absorbed when applied topically, and it is metabolized to pantothenic acid, which is then incorporated into various metabolic pathways. The pharmacokinetics of dexpanthenol, including its distribution, metabolism, and elimination, are influenced by the route of administration. Its efficacy in promoting wound healing is attributed to its ability to penetrate the skin and exert effects at the cellular level.

Pregnancy

Dexpanthenol is generally considered safe during pregnancy; however, its use should be based on a risk-benefit assessment by a healthcare provider.

Breast-feeding

Dexpanthenol is excreted in breast milk in small amounts. Caution is advised when administered to breastfeeding women, and its use should be evaluated in terms of potential benefits and risks.

Storage

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

Formulations

• Topical solution
• Cream
• Ointment

Indications

• Metabolic acidosis
• Lactic acidosis
• Energy substrate in critical illness
• Monitoring tissue perfusion and oxygenation

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to specific guidelines based on clinical context as dosing is highly variable and situation-dependent.

Mechanism of action

Lactate acts as a signaling molecule and energy substrate in various physiological and pathological processes. It is involved in the modulation of several metabolic pathways, including the Cori cycle and Krebs cycle. Lactate also participates in metabolic reprogramming, especially in cancer cells, where it can promote tumor growth and survival by providing an alternative energy source and influencing cellular signaling pathways such as the PI3K/AKT/mTOR pathway.

Pharmacodynamics

Lactate plays a vital role in energy metabolism. It can be oxidized back to pyruvate by lactate dehydrogenase, entering the Krebs cycle for ATP production. In addition to serving as an energy substrate, lactate impacts pH regulation and can influence the function of various immune cells. Its levels can indicate the state of oxygen delivery and utilization in tissues, thus serving as a marker for metabolic stress.

Pharmacokinetics

Lactate is produced primarily in the cytoplasm during glycolysis, with its concentration in the blood reflecting the balance between production and clearance. It is metabolized predominantly in the liver, where it can be converted back to glucose or utilized in the Krebs cycle. Lactate levels can vary based on factors such as exercise, tissue hypoxia, and metabolic conditions.

Pregnancy

Lactate is generally regarded as safe during pregnancy as it is a naturally occurring metabolite in the body, but specific clinical advice should be sought.

Breast-feeding

Lactate is considered safe during breastfeeding as it is a normal component of human metabolism, but consult a healthcare provider for personalized advice.

Storage

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

Indications

• Herpes simplex virus infections
• Lysine deficiency

Dosage

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

Adults: Refer to the BNF for specific dosage recommendations.

Mechanism of action

Lysine inhibits the viral replication of the herpes simplex virus by altering the amino acid ratio in the tissue culture media. A higher concentration of L-lysine compared to L-arginine has been shown to reduce viral growth and cytopathogenicity. Additionally, lysine facilitates calcium absorption from the small intestine and is involved in protein synthesis through its role in the tRNA charging process, linking amino acids to their corresponding tRNA for translation.

Pharmacodynamics

Lysine ensures adequate calcium absorption and is involved in the formation of collagen, essential for bone, cartilage, and connective tissues. It aids in the production of various biological molecules, including antibodies, hormones, and enzymes. Deficiency in lysine can manifest as tiredness, inability to concentrate, irritability, and other health issues.

Pharmacokinetics

Lysine is absorbed in the small intestine and is transported in the bloodstream to various tissues, where it participates in protein synthesis and other metabolic processes. The metabolism of lysine involves its degradation and utilization in various biosynthetic pathways.

Adverse effects

• Gastrointestinal upset
• Diarrhea
• Nausea
• Abdominal pain

Precautions

• Use with caution in individuals with kidney disease
• Consult a healthcare professional before use if pregnant or breastfeeding

Pregnancy

Safety in pregnancy has not been established. Consult a healthcare professional before use.

Breast-feeding

Lysine is generally considered safe in breastfeeding, but consult a healthcare professional before use.

Storage

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

Formulations

• Oral tablet
• Oral capsule
• Powder for oral solution

Indications

• Dermatitis
• Acne
• Rosacea
• Hyperpigmentation
• Skin aging

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines for paediatric patients.

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

Mechanism of action

Niacinamide functions primarily as a precursor to NAD and NADP, which are crucial for numerous enzymatic reactions in the body. It is involved in the NAD salvage pathway, which recycles nicotinamide for NAD synthesis. This process is vital for cellular energy production and metabolic processes. Niacinamide also has anti-inflammatory properties, which may contribute to its effects in skin health.

Pharmacodynamics

Niacinamide exhibits various pharmacological effects, including enhancing skin barrier function, reducing inflammation, and improving skin pigmentation. It has been shown to modulate keratinocyte function, improve collagen synthesis, and decrease the synthesis of sebum, thereby providing beneficial effects in conditions like acne and rosacea.

Pharmacokinetics

Niacinamide is readily absorbed from the gastrointestinal tract. It is distributed widely throughout the body and can cross biological membranes. The metabolism of niacinamide primarily occurs in the liver through methylation and conjugation, and it is excreted in urine as metabolites. The half-life of niacinamide is approximately 1-2 hours, and its effects can be prolonged due to its role in NAD synthesis.

Pregnancy

No evidence of harm, but use only if clearly needed.

Breast-feeding

Considered safe to use while breastfeeding.

Storage

Store in a cool, dry place away from light.

Formulations

• {'type': 'Topical cream', 'concentration': 'Various concentrations available'}
• {'type': 'Oral tablets', 'concentration': '100 mg, 250 mg, 500 mg'}

Indications

• Vitamin A deficiency
• Night blindness
• Impaired wound healing
• Epithelial disorders

Dosage

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

Adults: Refer to BNF for specific adult dosing information.

Mechanism of action

Retinol is converted in the retina to 11-cis-retinal, which is crucial for the conversion of light into neural signals necessary for vision. It binds to opsin in rhodopsin, facilitating the isomerization to all-trans-retinal upon exposure to light, thus triggering visual signaling. Additionally, retinol interacts with retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) as transcription factors, modulating gene expression related to cellular differentiation and growth.

Pharmacodynamics

Vitamin A is effective in treating Vitamin A deficiency, which can lead to vision impairment and other health issues. It plays a critical role in various biological processes including vision, cellular differentiation, reproduction, and immune system function. Its deficiency can cause symptoms such as night blindness and impaired wound healing, while adequate levels support growth and development.

Pharmacokinetics

Retinol is absorbed from the gastrointestinal tract and stored in the liver, where it can be mobilized as needed. It undergoes metabolism primarily in the liver, where it is converted to retinal and retinoic acid, the active forms of Vitamin A. The elimination half-life varies, but retinol is generally excreted in urine and bile. The bioavailability can be affected by dietary fat intake.

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Fatigue
• Irritability
• Dry skin
• Peeling of skin
• Itching
• Blurred vision

Precautions

• Use with caution in patients with liver disease due to potential hepatotoxicity.
• Monitor for signs of vitamin A toxicity, especially in patients on high doses or prolonged therapy.
• Caution in patients with a history of alcohol abuse, as it may exacerbate liver conditions.

Pregnancy

Retinol should be used with caution during pregnancy due to the risk of teratogenic effects. High doses of vitamin A can lead to fetal malformations.

Breast-feeding

Retinol is generally considered safe during breastfeeding, but excessive intake should be avoided to prevent potential adverse effects on the infant.

Storage

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

Formulations

• Capsules
• Tablets
• Oral solutions
• Topical preparations

Indications

• Riboflavin deficiency
• Migraine prevention
• Cataract prevention
• General health maintenance

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations for adults.

Mechanism of action

Riboflavin binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. It is converted into two coenzymes: flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential for various oxidative enzyme systems, facilitating hydrogen transport. The antioxidant activity of riboflavin is largely due to its role as a precursor of FAD, which is involved in producing reduced glutathione, a major antioxidant enzyme cofactor.

Pharmacodynamics

Riboflavin is easily absorbed and plays a key role in numerous physiological functions, including energy production, red blood cell formation, and growth regulation. It is vital for the maintenance of healthy skin and eyes and has a role in the prevention and treatment of eye disorders, including cataracts. Riboflavin also supports thyroid activity and general health.

Pharmacokinetics

Riboflavin is readily absorbed in the gastrointestinal tract and is distributed throughout the body. It is primarily excreted in urine, with excess amounts eliminated, as riboflavin is a water-soluble vitamin. The pharmacokinetics of riboflavin can vary based on dietary intake and individual physiological conditions.

Adverse effects

• No significant adverse effects reported with normal dietary intake
• High doses may lead to yellow-orange discoloration of urine
• Rarely, hypersensitivity reactions

Precautions

• Use with caution in patients with known hypersensitivity to riboflavin or any of its components
• Consult healthcare provider before starting high-dose riboflavin supplements

Pregnancy

Riboflavin is generally considered safe during pregnancy and is important for fetal development. Adequate intake is necessary to prevent deficiency.

Breast-feeding

Riboflavin is excreted in breast milk, and adequate maternal intake is important for infant health.

Storage

Store in a tightly closed container at room temperature, away from light and moisture.

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

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

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight. Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions. Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma. In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys. Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in en

Pharmacodynamics

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys.

Mechanism of action

Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which 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. This alcohol ... is said to increase the amount of coenzyme A available for the synthesis of acetylcholine. Increased formation of acetylcholine is thought to increase peristalsis and intestinal tone. ... To test the functional effect of pantothenate on dermal fibroblasts, cells were cultured and in vitro proliferation tests were performed using a standardized scratch test procedure. For all three donors analyzed, a strong stimulatory effect of pantothenate at a concentration of 20 ug/mL on the proliferation of cultivated dermal fibroblasts was observed. To study the molecular mechanisms resulting in the proliferative effect of pantothenate, gene expression was analyzed in dermal fibroblasts cultivated with 20 ug/mL of pantothenate compared with untreated cells using the GeneChip Human Exon 1.0 ST Array. A number of significantly regulated genes were identified including genes coding for interleukin (IL)-6, IL-8, Id1, HMOX-1, HspB7, CYP1B1 and MARCH-II. Regulation of these genes was subsequently verified by quantitative real-time polymerase chain reaction analysis. Induction of HMOX-1 expression by pantothenol and pantothenic acid in dermal cells was confirmed on the protein level using immunoblots. Functional studies revealed the enhanced suppression of free radical formation in skin fibroblasts cultured with panthenol. In conclusion, these studies provided new insight in the molecular mechanisms linked to the stimulatory effect of pantothenate and panthenol on the proliferation of dermal fibroblasts. /Calcium pantotenate/ ... Pantothenic acid, pantothenol and other derivatives ... are precursors of CoA /that/ protect cells and whole organs against peroxidative damage by increasing the content of cell glutathione...

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

Proteins of the herpes simplex virus are rich in L-arginine, and tissue culture studies indicate an enhancing effect on viral replication when the amino acid ratio of L-arginine to lysine is high in the tissue culture media. When the ratio of L-lysine to L-arginine is high, viral replication and the cytopathogenicity of herpes simplex virus have been found to be inhibited. L-lysine may facilitate the absorption of calcium from the small intestine. 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. /Amino acids/ 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. /Amino acids/

Pharmacodynamics

Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.

Mechanism of action

Vision:Vitamin A (all-<i>trans</i> retinol) is converted in the retina to the 11-<i>cis</i>-isomer of retinaldehyde or 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-<i>cis</i>-retinal, while attached to opsin in rhodopsin is isomerized to all-<i>trans</i>-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-<i>trans</i>-retinal is then released from opsin and reduced to all-<i>trans</i>-retinol. All-<i>trans</i>-retinol is isomerized to 11-<i>cis</i>-retinol in the dark, and then oxidized to 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-<i>cis</i> retinal rapidly. Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted. Topical vitamin A can reverse the impairment of wound healing seen in patients receiving corticosteroids, perhaps by restoring the normal inflammatory reaction in the wound. The possibility has been suggested that systemic vitamin A could inhibit the anti-inflammatory effect of systemic corticosteroids. Retinol arrested proliferation of cultured neuroblastoma cells at concentrations of 50 um. A correlation existed between inhibition of growth and inhibition of ornithine decarboxylase in both neuroblastoma cells and glioma cells with retinol. In rats exptl-hypervitaminosis A has been shown ... to produce severe damage of the retina, mainly in the pigment epithelium according to electron microscopy. Alcohol dehydrogenase activity was shown to disappear in the pigment epithelium and visual cells ... . /The authors/ have shown that in an experimental cell culture system consisting of carcinogen-treated 10T1/2 cells, both retinoids and all dietary carotenoids examined can reversibly inhibit neoplastic transformation in the post-initiation phase of carcinogenesis. This activity strongly correlates with their ability to increase gap junctional intercellular communication by up-regulating the expression of the gene CX43 (connexin43). Connexins comprise the structural unit of gap junctions, organelles which allow direct transfer of signals, nutrients and waste products between contacting cells. CX43 is the most widely expressed member of the gap junction family of genes, and we have demonstrated that its expression is strongly down-regulated in human cancers and in several premalignant conditions. When several human tumour cell lines were genetically engineered to conditionally express CX43 under the influence of a tetracycline promoter, their neoplastic phenotype was strongly attenuated. Specifically, induced cells were inhibited from growing in an anchorage-independent manner and, additionally, growth as xenografts in immunocompromised animals was also strongly attenuated. Growth inhibition in suspension was associated both with increased G(1) cell-cycle arrest and with increased apoptosis. /The authors/ propose a model whereby junctional communication allows the transfer of growth inhibitory signals from normal to neoplastic cells and that retinoids and carotenoids, by increasing signal transfer, act to prevent cancer.

Pharmacodynamics

Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-<i>trans</i> retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system.

Mechanism of action

Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase. Riboflavin is converted to 2 coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are necessary for normal tissue respiration. Riboflavin is also required for activation of pyridoxine, conversion of tryptophan to niacin, and may be involved in maintaining erythrocyte integrity. Riboflavin functions as the coenzyme for flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which primarily influence hydrogen transport in oxidative enzyme systems (eg, cytochrome C reductase, succinic dehydrogenase, xanthine oxidase). Two active forms of riboflavin exist ... coenzyme flavin mononucleotide (FMN) and coenzyme flavin adenine dinucleotide (FAD). They are formed by reaction of riboflavin with 1 and 2 molecules of ATP as follow: riboflavin + ATP = riboflavin-P (FMN) + ADP; FMN + ATP = riboflavin-ADP (FAD) + PP. Riboflavin is a water-soluble, yellow, fluorescent compound. The primary form of the vitamin is as an integral component of the coenzymes flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). It is in these bound coenzyme forms that riboflavin functions as a catalyst for redox reactions in numerous metabolic pathways and in energy production. ... The redox reactions in which flavocoenzymes participate include flavoprotein-catalyzed dehydrogenations that are both pyridine nucleotide (niacin) dependent and independent, reactions with sulfur-containing compounds, hydroxylations, oxidative decarboxylations (involving thiamin as its pyrophosphate), dioxygenations, and reduction of oxygen to hydrogen peroxide. There are obligatory roles of flavocoenzymes in the formation of some vitamins and their coenzymes. For example, the biosynthesis of two niacin-containing coenzymes from tryptophan occurs via FAD-dependent kynurenine hydroxylase, an FMN-dependent oxidase catalyzes the conversion of the 5'-phosphates of vitamin B6 to coenzymic pyridoxal 5'-phosphate, and an FAD-dependent dehydrogenase reduces 5,10-methylene-tetrahydrofolate to the 5'-methyl product that interfaces with the B12-dependent formation of methionine from homocysteine and thus with sulfur amino acid metabolism. For more Mechanism of Action (Complete) data for Riboflavin (7 total), please visit the HSDB record page.

Pharmacodynamics

Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts.