FERTIPRO+ TABLETS

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Abdominal distension
• Decreased appetite
• Flatulence
• Nausea

Interactions

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Indications

• Vitamin B6 deficiency
• 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

• 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

• Selenium deficiency
• Supportive therapy in conditions requiring antioxidant support
• Potential adjunct in cancer prevention strategies

Dosage

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

Adults: Initially 100–500 micrograms daily, adjusted according to response and serum levels.

Mechanism of action

Selenium is metabolized to selenophosphate and selenocysteine, which are essential for the synthesis of selenoproteins. This process involves the incorporation of selenium into proteins through a specialized tRNA that recognizes the RNA sequence UGA, which is facilitated by SECIS structures and SBP-2 proteins. Key selenoproteins, like glutathione peroxidases, help protect cells from oxidative damage, thus playing a significant role in reducing the risk of diseases such as atherosclerosis and certain cancers.

Pharmacodynamics

Selenium is incorporated into various selenoproteins that perform essential functions, including antioxidant activity, redox balance, and regulation of thyroid hormones. Its role in antioxidant defense mechanisms is particularly important for protecting cells against reactive oxygen species (ROS). Selenium supplementation has been linked to improved immune function and potential cancer prevention.

Pharmacokinetics

Selenium is absorbed through the gastrointestinal tract, and its bioavailability can vary based on the source and form of selenium. Once absorbed, it is distributed to various tissues, where it is incorporated into selenoproteins. Selenium is primarily excreted through urine, and its half-life can depend on dietary intake and individual metabolism. Selenium status can be assessed through blood levels of selenoproteins and selenium itself.

Adverse effects

• Nausea
• Anaemia
• Aplastic anaemia
• Skin reactions
• Gastrointestinal disorders

Precautions

• Selenium supplementation should not be given unless there is good evidence of deficiency.
• Use caution in patients with a history of hypersensitivity to selenium or its compounds.

Pregnancy

Limited information is available regarding selenium supplementation during pregnancy. Consult specialist sources for guidance.

Breast-feeding

Limited information is available; the effect of selenium on copper levels in milk is conflicting, and its impact on the infant is unknown.

Storage

After opening, store in a refrigerator (2–8°C).

Formulations

• Tablets (e.g., L-Selenomethionine 200 micrograms, SelenoPrecise 100 micrograms)
• Capsules (e.g., Trientine dihydrochloride 250 mg)
• Injection solutions (e.g., Sodium selenite 50 micrograms per 1 ml)

Indications

• Menstrual disorders
• Menopause symptoms
• Anemia
• Hormonal balance
• Circulatory issues

Dosage

Children: Refer to specific herbal product guidelines, as safety and efficacy in children have not been well established.

Adults: Refer to specific herbal product guidelines as doses can vary widely based on formulation and preparation.

Mechanism of action

The exact mechanism of action of dong quai is not fully understood. However, it is believed to exert its effects through modulation of estrogenic activity, enhancing blood circulation, and possessing anti-inflammatory properties. The presence of compounds like ferulic acid may influence the synthesis and metabolism of hormones, particularly estrogen, while other constituents may promote vasodilation and improve microcirculation.

Pharmacodynamics

Dong quai exhibits various pharmacodynamic effects, including potential estrogenic activity, which may help alleviate symptoms associated with hormonal imbalances such as hot flashes and menstrual discomfort. Additionally, its anti-inflammatory properties may contribute to overall wellness and pain relief. The herb may also have a role in promoting hematopoiesis, or the production of blood cells, which could be beneficial in conditions like anemia.

Pharmacokinetics

The pharmacokinetics of dong quai are not well characterized in terms of absorption, distribution, metabolism, and excretion. However, it is known that the active compounds are absorbed in the gastrointestinal tract. The bioavailability of these compounds may be affected by their solubility and interaction with other dietary components. Dong quai is metabolized in the liver, and its effects may vary based on the preparation method and the presence of other herbs in traditional formulations.

Pregnancy

There is insufficient reliable information on the safety of dong during pregnancy. It is recommended to avoid its use unless prescribed by a healthcare professional.

Breast-feeding

Limited data is available regarding the excretion of dong components in breast milk. Caution is advised when using this product while breastfeeding.

Storage

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

Indications

• General wellness support
• Anti-inflammatory effects
• Antioxidant activity
• Digestive aid
• Support for immune function

Dosage

Children: Paediatric dosing should be determined based on the specific extract and its intended use. Consultation with a healthcare provider is recommended for accurate dosing.

Adults: Dosage varies widely depending on the specific extract and formulation. It is essential to follow the manufacturer's instructions or consult a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action of herbal extracts can vary significantly based on their constituents. Commonly, they exert their effects through multiple pathways including modulation of neurotransmitter systems, interference with inflammatory processes, or direct antioxidant activity. Some extracts may activate certain receptors or inhibit enzymes related to disease processes.

Pharmacodynamics

The pharmacodynamics of extracts is complex due to the presence of multiple active compounds which can have synergistic or antagonistic effects. These compounds may influence cellular signaling pathways, alter gene expression, or modulate immune response. The overall pharmacological profile is determined by the specific composition of the extract, its concentration, and the biological target it interacts with.

Pharmacokinetics

The pharmacokinetics of extracts involves absorption, distribution, metabolism, and excretion of the active compounds. Generally, herbal extracts are absorbed in the gastrointestinal tract, with bioavailability influenced by factors such as formulation, the presence of food, and individual metabolic differences. Compounds may undergo hepatic metabolism, and elimination can occur through urine or feces, depending on their chemical nature.

Pregnancy

Consult a healthcare professional before use, as the safety of the extract during pregnancy has not been established.

Breast-feeding

Consult a healthcare professional before use, as the safety of the extract during breastfeeding has not been established.

Storage

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

Indications

• Folate deficiency
• Megaloblastic anemia
• Prevention of neural tube defects in pregnancy
• Supplementation in patients on certain medications (e.g., methotrexate)

Dosage

Children: Refer to the BNF for Children for appropriate pa

Adults: Refer to specific guidelines or the BNF for appropriate adult dosing based on the indication.

Mechanism of action

Folate functions as a coenzyme in the conversion of homocysteine to methionine, a process that is vital for DNA synthesis and repair. It is involved in the one-carbon metabolism pathway, where it acts as a carrier of one-carbon units necessary for the synthesis of purines and thymidylate, thus supporting the production of nucleotides and DNA. This mechanism is particularly important in rapidly dividing cells.

Pharmacodynamics

Folate is critical for the formation of red blood cells and the proper functioning of the nervous system. It aids in the production of nucleic acids, which are essential for cell proliferation. Folate deficiency can lead to impaired DNA synthesis, resulting in megaloblastic anemia characterized by the presence of large, immature red blood cells in the bloodstream. Adequate folate levels are also associated with reduced risk of neural tube defects in developing fetuses.

Pharmacokinetics

Folate is absorbed in the proximal part of the small intestine, primarily in the jejunum, and is transported in the bloodstream bound to plasma proteins. It undergoes hepatic metabolism and is stored mainly in the liver. The elimination half-life varies, but dietary folate can be retained in the body for several weeks. Excess folate is excreted through the urine. The bioavailability of folate from food sources is lower compared to synthetic folic acid found in supplements.

Interactions

• folates+fluorouracil: Severe (increases risk of toxicity)
• folates+antiepileptics: Moderate (decreases concentration)
• folates+fosphenytoin: Moderate (decreases concentration)
• folates+phenobarbital: Moderate (decreases concentration)
• folates+phenytoin: Moderate (decreases concentration)
• folates+primidone: Moderate (decreases concentration)
• sulfasalazine+folates: Unknown (decreases absorption)

Pregnancy

Folate is essential for fetal development and is often recommended to prevent neural tube defects.

Breast-feeding

Folate is generally safe during breastfeeding, as it is important for both maternal and infant health.

Storage

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

Formulations

• Tablets
• Injection

Indications

• Fatigue
• Stress management
• Cognitive enhancement
• Immune support
• General well-being

Dosage

Children: Refer to specific product guidelines, as dosing in children should be determined by a healthcare professional.

Adults: Refer to specific product guidelines, as dosing can vary based on formulation and intended use.

Mechanism of action

Ginseng is thought to exert its effects through several mechanisms, including modulation of the hypothalamic-pituitary-adrenal (HPA) axis, enhancement of antioxidant activity, and regulation of neurotransmitter levels. Ginsenosides, the active compounds in ginseng, may influence cellular signaling pathways, promote neuroprotection, and enhance immune responses.

Pharmacodynamics

The pharmacodynamic effects of ginseng are attributed primarily to its active constituents, ginsenosides, which interact with various receptors and enzymes in the body. These interactions can lead to increased energy metabolism, improved cognitive function, enhanced physical performance, and modulation of the immune system. Ginseng may also exhibit adaptogenic properties, helping the body to maintain homeostasis under stress.

Pharmacokinetics

Ginsenosides undergo extensive metabolism in the body, primarily by the liver. Bioavailability can vary significantly based on the specific ginsenoside and the method of administration. Ginseng is usually administered orally, with effects typically observed within several hours after ingestion. The elimination half-life of ginsenosides can vary based on the specific compound and individual metabolism, with some studies suggesting that effects may persist for several hours to days.

Adverse effects

• Insomnia
• Headache
• Gastrointestinal disturbances
• Nervousness
• Hypertension
• Allergic reactions

Interactions

• May interact with anticoagulants (e.g., warfarin)
• May enhance the effects of caffeine
• May affect insulin levels and blood sugar control
• Potential interaction with immunosuppressants

Precautions

• Use with caution in patients with hypertension
• May cause sleep disturbances; avoid use before bedtime
• Should be used cautiously in patients with diabetes
• Consult a healthcare provider before use in individuals with autoimmune conditions

Pregnancy

Limited data available. Generally not recommended due to potential hormonal effects.

Breast-feeding

Limited data available. Consult a healthcare provider before use.

Storage

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

Formulations

• Dried root
• Powdered extract
• Capsules
• Tinctures
• Teas

Indications

• Wound healing
• Skin ulceration
• Burns
• Psoriasis
• Dermatitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age and condition.

Adults: Refer to the BNF for specific formulations and dosing guidelines, as dosages may vary based on the condition being treated and the formulation used.

Mechanism of action

While there is no well-controlled data to formally substantiate the method of action, ongoing studies suggest that allantoin may induce a histological wound healing profile in animal models, leading to improved reestablishment of normal skin. This includes increased vasodilation, inflammatory cell presence, angiogenesis, fibroblast proliferation, and collagen deposition in treated wounds compared to untreated ones.

Pharmacodynamics

There is limited controlled data regarding the pharmacodynamic properties of allantoin. However, studies indicate that allantoin may possess moisturizing and keratolytic effects, increasing the extracellular matrix's water content and enhancing the desquamation of dead skin cells. These activities can promote cell proliferation and facilitate wound healing.

Pharmacokinetics

Specific pharmacokinetic data for allantoin in humans is limited. However, it is known to be applied topically, which suggests local absorption at the site of application. Systemic absorption is considered minimal due to its low molecular weight and hydrophilicity.

Pregnancy

There is limited data on the safety of allantoin in pregnancy. It is advisable to consult a healthcare professional before use.

Breast-feeding

Allantoin is generally considered safe during breastfeeding, but caution is recommended. Consult a healthcare professional before use.

Storage

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

Formulations

• Topical cream
• Gel
• Ointment

Mechanism of action

Levocarnitine acts as a carrier molecule for long-chain fatty acids, transporting them into mitochondria for beta-oxidation, which is critical for energy production. It also exports acyl groups from subcellular organelles and cells to urine, preventing toxic accumulation. The mechanism of action includes interactions with carnitine transporters, translocases, and acetyltransferases. Additionally, it normalizes the brain's redox state and enhances urea synthesis in the liver, potentially activating the glucocorticoid receptor. L-carnitine's antagonistic effects on thyroid hormone action, including inhibiting its nuclear entry, contribute to its therapeutic applications.

Pharmacodynamics

Levocarnitine plays a significant role in lipid metabolism and energy production through its involvement in the transport of fatty acids into the mitochondria. A deficiency in carnitine can lead to various metabolic issues, including liver, heart, and muscle dysfunction. The therapeutic use of levocarnitine includes its ability to stimulate gastric and pancreatic secretions and treat hyperlipoproteinemias. The L-isomer of carnitine is specifically active in lipid metabolism, and its deficiency can be identified through biochemical markers such as low plasma concentrations of free carnitine and elevated acylcarnitine levels.

Pharmacokinetics

Levocarnitine is absorbed in the intestines and distributed throughout the body tissues. It is primarily metabolized in the liver, with excretion occurring via urine. The pharmacokinetics of levocarnitine can vary based on dietary intake, physiological status, and specific health conditions that may affect its metabolism and clearance. The bioavailability of levocarnitine may also be

Adverse effects

• Nausea
• Vomiting
• Abdominal cramps
• Diarrhea
• Fishy body odor
• Rash
• Seizures (rare)

Interactions

• Anticoagulants may have altered effects.
• Thyroid hormones may have altered action due to L-carnitine's peripheral antagonism.

Precautions

• Use with caution in patients with renal impairment.
• Monitor for potential interactions with other medications.

Pregnancy

Limited data is available on the use of levocarnitine during pregnancy. Use only if clearly needed and after assessing benefits versus risks.

Breast-feeding

Levocarnitine is excreted in human milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Oral solution
• Tablets
• Capsules

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

Dosage

Children: Refer to specific formulations and preparations for recommended dosing in children, as it varies widely by plant and intended use.

Adults: Refer to specific formulations and preparations for recommended dosing, as it varies widely by plant and intended use.

Mechanism of action

The mechanism of action varies significantly depending on the specific root being referred to. Many plant roots contain bioactive compounds such as alkaloids, flavonoids, and glycosides, which can modulate various biochemical pathways in the body. For instance, certain roots may inhibit enzymes involved in inflammation or microbial growth, while others may enhance immune responses or modulate neurotransmitter activity.

Pharmacodynamics

Pharmacodynamics will differ based on the specific root and its active compounds. Generally, roots may exhibit anti-inflammatory, analgesic, antimicrobial, or antioxidant effects. The pharmacodynamic profile will also depend on factors such as dosage, preparation method (e.g., decoction, tincture), and the specific condition being treated. For example, some roots may interact with cellular receptors, while others may exert their effects through modulation of gene expression.

Pharmacokinetics

The pharmacokinetics of a root extract will vary with the specific plant. Typically, factors such as absorption, distribution, metabolism, and excretion are influenced by the chemical composition of the root, the method of preparation, and the route of administration. Many active compounds are absorbed in the gastrointestinal tract, metabolized in the liver, and excreted via urine or feces. The bioavailability of these compounds can be affected by their solubility and stability.

Pregnancy

The safety of root during pregnancy has not been established. Consult a healthcare professional before use.

Breast-feeding

It is unknown whether root is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

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.

Mechanism of action

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

Pharmacodynamics

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

Mechanism of action

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA. This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality. The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS). The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein. Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function. Converging data from epidemiological, ecological, and clinical studies have shown that selenium (Se) can decrease the risk for some types of human cancers. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se compounds alter the expression and/or activities of signaling molecules, mitochondria-associated factors, transcriptional factors, tumor suppressor genes, and cellular reduced glutathione. Mechanistic studies have demonstrated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, whereas the hydrogen selenide pool with excess of selenoprotein synthesis can lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic events, it should be remembered that the chemical forms and the dose of Se, and the experimental system used, are determinants of its biological activities. This mini-review focuses on elucidation of the molecular mechanisms of cancer prevention by Se with the apoptotic approach. /Selenium/ Selenium status can also influence thyroid hormone function via the deiodinase enzymes. Selenium is a critical component of the deiodinase enzymes, including iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the active circulating form, triiodothyronine (T3). Selenium is also a component of GPX, the main enzyme responsible for protecting thyroid cells against oxidative damage. GPX is involved in the detoxification of hydrogen peroxide, which is produced in the thyroid during the conversion of T4 to T3. /Selenium/ Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially when the concentration of selenium is high and the concentration of sulfur is low in the organism. Inactivation of the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration, through effects on mitochondrial and microsomal electron transport, might contribute to acute selenium toxicity. Selenium may have a role in hepatic heme metabolism that is related to GPX or lipid peroxidation. Selenocysteine is specifically found in some proteins (e.g., glutathione peroxidase); selenomethionine appears to randomly substitute for methionine in protein synthesis. This appears to be an additional mechanism for intermediate- or chronic-duration toxicity. Skin, hair, and nail damage are significant indicators of chronic selenium overexposure. The mechanism causing these integumentary effects is unclear, but could be related to the high selenium concentrations in these tissues as a consequence of the substitution of selenium for sulfur in certain amino acids, including the disulfide bridges that pr

Pharmacodynamics

Selenium is incorporated into many different selenoproteins which serve various functions throughout the body.

Mechanism of action

There is no well controlled data that can formally substantiate the method of action. However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin. This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration.

Pharmacodynamics

There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing.

Mechanism of action

Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases. L-Carnitine is a peripheral antagonist of thyroid hormone action in some tissues. It inhibits thyroid hormone entry into cell nuclei. In a controlled clinical trial, L-carnitine was shown to reverse or prevent some symptoms of hyperthyroidism. ... Mortality and metabolic consequences of acute ammonium intoxication in mice are reduced by pharmacologic admin of L-carnitine. The mechanism for this effect may have 2 components. L-Carnitine admin normalizes the redox state of the brain (perhaps by incr the avail of beta-hydroxybutyrate and/or acetyl-L-carnitine to the brain), and it incr the rate of urea synth in the liver, perhaps in part by activation of the glucocorticoid receptor. At least part of the protective effect is associated with flux through the carnitine acyltransferases, as analogs of L-carnitine that are competitive inhibitors of carnitine acyltransferases enhance the toxicity of acute ammonium admin. Thus, it has been proposed that L-carnitine incr urea synth in the liver by facilitating fatty acid entry into mitochondria, leading to incr flux through the beta-oxidation pathway, an incr of intramitochondrial reducing equivalents, and enhancement of ATP production. ... Levocarnitine is necessary for normal mammalian fat utilization and energy metabolism. It facilitates entry of long-chain fatty acids into cellular mitochondria, where they are used during oxidation and energy production. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Carnitine's primary mechanism of action is apparently attributable to its role as a cofactor in the transformation of free long-chain fatty acids into acylcarnitines for subsequent transport into the mitochondrial matrix. Carnitine is involved in the metabolism of ketones for energy and the conversion of branched-chain amino acids - valine, leucine, and isoleucine - into energy. /Carnitine/ L-Carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... /This reaction facilitates the/ transfer of long-chain fatty acids from cytoplasm ... /and/ chain-shortened /very-long-chain/ fatty acids from peroxisomes to mitochondria /and the/ modulation of the acyl-CoA/CoA ratio in cellular compartments.

Pharmacodynamics

Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.

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

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.