OLIGOCARE TABLETS

Indications

• Iron deficiency anemia
• Prophylaxis of iron deficiency in at-risk populations
• Epithelial tissue changes such as atrophic glossitis and koilonychia

Dosage

Children: For children aged 1 month to 11 years: 0.25 mL per kilogram twice daily, with the total daily dose possibly given in 3 divided doses, not exceeding 20 mL per day. For children aged 12-17 years: 10 mL once daily.

Adults: The dose is calculated according to body weight and the iron deficit, specifying both the iron salt and formulation. For specific dosing, consult product literature.

Mechanism of action

Iron is necessary for the production of hemoglobin. Iron deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia. Ferrous fumarate releases iron in the gastrointestinal tract, facilitating its absorption and subsequent incorporation into hemoglobin, thus alleviating anemia.

Pharmacodynamics

The major activity of supplemental iron, including ferrous fumarate, is in the prevention and treatment of iron deficiency anemia. Iron also has putative immune-enhancing, anticarcinogenic, and cognition-enhancing activities, supporting overall health and functionality.

Pharmacokinetics

Ferrous fumarate is absorbed in the gastrointestinal tract, with absorption being optimal in an acidic environment. The bioavailability can be influenced by dietary factors, such as the presence of certain foods or medications that may inhibit iron absorption. Once absorbed, iron is transported in the blood bound to transferrin and is stored in tissues as ferritin and hemosiderin. The elimination half-life of iron is variable and depends on the individual's iron status and the amount of iron stored.

Contra-indications

• Iron overload syndromes
• Repeated blood transfusions
• Porphyria cutanea tarda

Adverse effects

• Asthenia
• Drowsiness
• Urine discoloration
• Cold sweat
• Confusion
• Decreased level of consciousness
• Thrombophlebitis
• Headache
• Joint stiffness
• Pain in extremities
• Skin reactions
• Small intestinal bacterial overgrowth
• Thirst
• Nausea
• Constipation
• Diarrhea
• Decreased appetite

Interactions

• Iron absorption may be affected by antacids and certain medications that alter gastric pH.

Precautions

• Monitor iron status to avoid iron overload.
• Caution in patients with intestinal strictures or diverticular disease.
• Care in elderly patients and those on high doses.

Pregnancy

Iron is generally considered safe during pregnancy, but supplementation should be monitored to avoid overload.

Breast-feeding

Iron supplementation may be necessary for exclusively breast-fed infants if maternal iron stores are low.

Storage

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

Formulations

• Solution for injection (Iron as Iron sucrose 20 mg per 1 ml)
• Capsules containing iron formulations

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

• Iron-deficiency anemia (therapeutic)
• Iron-deficiency anemia (prophylactic)

Dosage

Children: For children aged 1 month to 11 years: 0.25 mL/kilogram twice daily. For children aged 12 to 17 years: 10 mL once daily.

Adults: 280 mg twice daily.

Mechanism of action

Ferrous sulfate acts as a source of iron, which is essential for the synthesis of hemoglobin, the protein in red blood cells that carries oxygen. Iron is absorbed in the intestines, where it is converted into a form that can be incorporated into hemoglobin. The mechanism involves transport proteins that facilitate iron uptake and incorporation into the heme group of hemoglobin.

Pharmacodynamics

The pharmacodynamic effect of ferrous sulfate is the increase in hemoglobin levels and improvement in symptoms of anemia, such as fatigue and weakness. Iron supplementation leads to increased erythropoiesis (red blood cell production) in the bone marrow, effectively correcting the deficit in iron stores and enhancing oxygen-carrying capacity.

Pharmacokinetics

Ferrous sulfate is absorbed in the gastrointestinal tract, particularly in the duodenum and proximal jejunum. The bioavailability of iron from ferrous sulfate can be affected by dietary factors, with enhanced absorption in acidic environments. Peak plasma concentrations typically occur within 2 to 6 hours post-administration. Iron is primarily stored in the liver and bone marrow, and any excess iron is excreted through feces, urine, and sweat.

Contra-indications

• Hypersensitivity to ferrous sulfate or any of its excipients
• Hemochromatosis
• Hemosiderosis
• Thalassemia
• Other anemias not due to iron deficiency

Adverse effects

• Gastrointestinal disturbances (nausea, constipation, diarrhea, abdominal pain)
• Dark stools
• Staining of teeth (with liquid formulations)
• Allergic reactions (rare)

Interactions

• Antacids may reduce the absorption of iron
• Tetracycline antibiotics may interfere with iron absorption
• Ascorbic acid (vitamin C) may enhance iron absorption
• Certain foods and beverages (e.g., tea, coffee, dairy) can decrease iron absorption

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor for signs of iron overload
• Assess the cause of anemia before initiation of therapy
• Keep out of reach of children to prevent accidental overdose

Pregnancy

Ferrous sulfate is generally considered safe for use during pregnancy to prevent or treat iron-deficiency anemia.

Breast-feeding

Ferrous sulfate is excreted in breast milk in small amounts but is considered safe for breastfeeding mothers.

Storage

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

Formulations

• Ferrous sulfate 200 mg tablets
• Ferrous sulfate 325 mg modified-release tablets
• Ferrous sulfate oral solution 140 mg/5 mL
• Ferrous sulfate drops

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

• Improving bioavailability of poorly soluble drugs
• Controlled release of active ingredients
• Taste masking of bitter medications

Dosage

Children: Dosage for paediatric patients should be determined based on the active ingredient and specific formulation. Consult relevant pediatric guidelines or the BNF for Children.

Adults: Dosage varies depending on the active ingredient encapsulated in the beadlets. Refer to specific product guidelines for details.

Mechanism of action

The mechanism of action of beadlets largely depends on the active pharmaceutical ingredient they encapsulate. Beadlets are designed to release the drug at a specific rate, which can enhance absorption and therapeutic efficacy. The encapsulation can protect sensitive compounds from degradation and improve their solubility, leading to better bioavailability.

Pharmacodynamics

Pharmacodynamics of beadlets is contingent upon the pharmacological properties of the active ingredient they contain. Generally, beadlets allow for controlled drug release, improved absorption kinetics, and enhanced therapeutic effects. The release characteristics can vary based on the formulation and coating materials used, which can influence the onset and duration of action.

Pharmacokinetics

The pharmacokinetics of beadlets are influenced by the properties of the drug they deliver, such as its solubility, permeability, and metabolic stability. Upon administration, beadlets can dissolve in the gastrointestinal tract, leading to the release of the active ingredient. The rate of release and subsequent absorption can vary, impacting peak plasma concentrations and overall bioavailability. Factors such as beadlet size, coating materials, and the presence of excipients may also affect the pharmacokinetics.

Pregnancy

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

Breast-feeding

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

Storage

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

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

• 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

• Iron deficiency anemia
• Iron deficiency due to inadequate dietary intake
• Anemia associated with chronic disease
• Pregnancy-related anemia

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations, generally, adults may require 100-200 mg of elemental iron daily divided into several doses.

Mechanism of action

Ferrous ions (Fe2+) play a vital role in hemoglobin production by participating in the synthesis of heme, the iron-containing compound essential for oxygen transport in the blood. In addition, iron is a cofactor for various enzymes involved in metabolic pathways, including those related to DNA synthesis and energy production.

Pharmacodynamics

The pharmacodynamic effects of ferrous include increased hemoglobin synthesis, improved oxygen transport, and enhanced cellular energy metabolism. Supplementation leads to an increase in serum ferritin levels and replenishment of iron stores in the body, which is particularly beneficial in cases of iron deficiency anemia.

Pharmacokinetics

Ferrous iron is absorbed primarily in the duodenum and upper jejunum of the small intestine. The absorption rate can be influenced by various factors, including the presence of food, the form of iron, and individual patient characteristics. Once absorbed, ferrous is transported in the bloodstream bound to transferrin, and it is stored in the liver, spleen, and bone marrow as ferritin. The elimination half-life of iron is not well-defined as it is not excreted directly but rather recycled in the body.

Pregnancy

Not contraindicated, but iron supplementation should be done under medical supervision.

Breast-feeding

Iron is excreted in breast milk, but supplementation is generally considered safe.

Storage

Store in a cool, dry place away from 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

• Ox

Mechanism of action

Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It plays a role in hepatic biotransformation and detoxification, acting as a hydrophilic molecule added to lipophilic toxins for biliary excretion. GSH detoxifies methylglyoxal, a toxic metabolic by-product, via glyoxalase enzymes, converting it to less harmful substances. It also participates in conjugation and reduction reactions catalyzed by glutathione S-transferase enzymes, and can non-enzymatically conjugate with certain chemicals, such as N-acetyl-p-benzoquinone imine (NAPQI), detoxifying it in the process.

Pharmacodynamics

Glutathione plays a vital role in cellular defense against oxidative stress by neutralizing free radicals and reactive oxygen species. It is involved in maintaining the redox state of cells, which is critical for various cellular functions. The antioxidant properties of glutathione help in preventing cellular damage, modulating inflammatory responses, and regulating immune functions. Its ability to conjugate with xenobiotics enhances their solubility and facilitates their excretion, thereby contributing to detoxification processes in the liver.

Pharmacokinetics

Glutathione is synthesized in the body from its constituent amino acids, and its levels can be influenced by dietary intake and the body's oxidative stress status. Once synthesized, glutathione is distributed throughout the body, particularly in the liver, where it participates in detoxification processes. It is metabolized primarily in the liver, with its conjugation products being excreted via bile or urine. The half-life of glutathione can vary depending on the physiological and pathological conditions, and its levels can be influenced by factors such as age, diet, and the presence of diseases.

Pregnancy

There are no well-controlled studies of glutathione in pregnant women. Use only if clearly needed.

Breast-feeding

Use with caution. The effects of glutathione on nursing infants are not well known.

Storage

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

Formulations

• Injectable solution
• Oral supplement

Indications

• Cardiovascular diseases
• Erectile dysfunction
• Peripheral arterial disease
• Wound healing
• Muscle growth and recovery
• Immune system support

Dosage

Children: For paediatric dosing, it is important to refer to the BNF for Children for appropriate guidelines based on the child's age, weight, and clinical condition.

Adults: The typical dosage for adults varies based on the condition being treated, but common oral doses range from 2 to 30 grams per day, divided into multiple doses. For specific dosing recommendations, please refer to the BNF.

Mechanism of action

L-arginine is converted to nitric oxide by nitric oxide synthase (NOS), which is crucial for vascular function and blood flow regulation. NO activates guanylate cyclase, leading to increased levels of cyclic GMP, a secondary messenger that mediates vasodilation and other cellular responses. This pathway is vital in both the cardiovascular and immune systems, with different isoforms of NOS (eNOS, nNOS, iNOS) contributing to various physiological effects.

Pharmacodynamics

L-arginine has been shown to enhance immune responses, improve wound healing, stimulate growth hormone release, and support muscle hypertrophy and tissue repair. Its role in nitric oxide production aids in vasodilation, improving blood circulation and oxygen delivery to tissues, which is essential for recovery and regeneration.

Pharmacokinetics

L-arginine is absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is metabolized primarily in the liver and kidneys, with a half-life of approximately 1-2 hours. The bioavailability of L-arginine can be influenced by dietary intake and metabolic conditions.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Diarrhea
• Abdominal pain
• Hypotension
• Allergic reactions

Interactions

• Antihypertensive agents may have additive effects leading to increased hypotension
• Sildenafil and other medications for erectile dysfunction may have enhanced effects when used with L-arginine

Precautions

• Caution in patients with a history of asthma or allergies
• Use with caution in patients with hypotension
• Monitor blood pressure in patients taking antihypertensive medications

Pregnancy

The safety of L-arginine in pregnancy has not been established. Consult a healthcare provider before use.

Breast-feeding

L-arginine is excreted in breast milk, and its safety during breastfeeding is not well established. Consult a healthcare provider.

Storage

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

Formulations

• Oral tablets
• Powder for oral solution
• Capsules

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

• Dietary supplement for antioxidant support
• Potential risk reduction for prostate cancer
• Potential risk reduction for lung cancer

Dosage

Children: Refer to specific guidelines as dosing can vary based on the formulation and purpose of use.

Adults: Refer to specific guidelines as dosing can vary based on the formulation and purpose of use.

Mechanism of action

Lycopene functions as a very potent antioxidant, trapping singlet oxygen and reducing mutagenesis. It inhibits cancer cell growth by disrupting growth factor receptor signaling and cell cycle progression. Lycopene upregulates connexin 43, enhancing gap junctional communication which is often deficient in tumors. Furthermore, it exhibits synergistic effects on cell proliferation and differentiation when combined with 1,25-dihydroxyvitamin D3, indicating interactions at a nuclear or subcellular level.

Pharmacodynamics

Lycopene's antioxidant properties play a critical role in protecting cells from oxidative stress. By trapping reactive oxygen species, it lessens cellular damage and may help to prevent the initiation and progression of cancer. Its ability to modulate cell signaling pathways and improve gap junction communication contributes to its anticancer effects. The interactions with vitamin D3 suggest a complex role in regulating cellular functions.

Pharmacokinetics

Lycopene is absorbed in the intestine and can be detected in the serum and various tissues. Its bioavailability can be influenced by dietary factors, including fat intake, which enhances absorption. Once in the body, lycopene is stored in adipose tissue and the liver. The elimination half-life and exact metabolic pathways are not well defined, but it is believed to undergo some conversion into other metabolites before excretion.

Pregnancy

There is insufficient reliable information regarding the safety of lycopene during pregnancy. Caution is advised.

Breast-feeding

Lycopene is considered safe during breastfeeding, but data on its excretion in human milk is limited.

Storage

Store in a cool, dry place, away from light.

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 B12 deficiency
• Megaloblastic anemia
• Peripheral neuropathy
• Neuropathic pain
• Multiple sclerosis

Dosage

Children: For paediatric patients, refer to the BNF for Children for appropriate dosing guidelines.

Adults: The typical adult dosage for methylcobalamin is 500 micrograms to 1,000 micrograms administered intramuscularly or subcutaneously, usually once daily for the initial treatment, followed by maintenance doses as needed.

Mechanism of action

Methylcobalamin serves as a cofactor for the enzyme methionine synthase, which catalyzes the conversion of homocysteine to methionine. This reaction is crucial in the synthesis of S-adenosylmethionine (SAMe), an important methyl donor in numerous methylation reactions within the body. Methylcobalamin also plays a role in myelin formation and the maintenance of nerve cells.

Pharmacodynamics

Methylcobalamin exhibits neuroprotective effects, promoting nerve regeneration and repair in peripheral neuropathy. It is believed to enhance nerve conduction and improve neurological function. The physiological effects are primarily attributed to its role in methylation processes and the synthesis of neurotransmitters.

Pharmacokinetics

Methylcobalamin is water-soluble and is absorbed in the intestine. The bioavailability can be affected by gastrointestinal health, and intrinsic factor is not required for its absorption. It is distributed throughout the body, with high concentrations in the liver, kidneys, and brain. The elimination half-life of methylcobalamin is approximately 6 hours, and it is excreted primarily in the urine.

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Anxiety
• Rash
• Pruritus

Precautions

• Monitor patients with Leber's disease due to potential optic nerve damage.
• Caution in patients with allergies to cobalt or vitamin B12.
• Use with caution in patients with renal impairment.

Pregnancy

Methylcobalamin is classified as a category A drug. It is generally considered safe during pregnancy, but consultation with a healthcare provider is recommended.

Breast-feeding

Methylcobalamin is excreted in breast milk. It is generally considered safe during breastfeeding, but consultation with a healthcare provider is recommended.

Storage

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

Formulations

• Tablets
• Injections
• Sublingual tablets
• Oral solutions

Dosage

Children: Refer to the specific drug formulation and clinical guidelines for appropriate dosing. Pediatric doses should be carefully calculated based on the active ingredient and the child's age and weight.

Adults: Refer to the specific drug formulation and clinical guidelines for appropriate dosing. Doses can vary widely based on the active ingredient and its clinical application.

Mechanism of action

Pentahydrate forms do not have a specific mechanism of action, as they are typically salts or hydrates of other active compounds. The effectiveness depends on the active ingredient associated with the pentahydrate form, which may engage in various biochemical interactions in the body to exert therapeutic effects. Generally, the release of the active drug from its hydrated form can influence its absorption and subsequent pharmacological activity.

Pharmacodynamics

The pharmacodynamics of pentahydrate forms is determined by their active ingredients. The hydration state can affect the dissolution rate, which in turn influences the onset of action and overall efficacy. Hydrated forms can improve solubility in biological fluids, leading to enhanced absorption and bioavailability in certain cases. The specific pharmacological action, such as receptor binding or enzyme inhibition, will depend on the drug itself rather than the pentahydrate status.

Pharmacokinetics

The pharmacokinetics of pentahydrate forms is influenced by the solubility and stability of the drug. Generally, a hydrated form may result in increased dissolution rates, promoting better absorption in the gastrointestinal tract. The extent and rate of absorption can vary based on the specific pentahydrate and its active ingredient. Distribution, metabolism, and excretion will depend on the nature of the drug itself, including its half-life and the pathways involved in its elimination from the body.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the risk.

Breast-feeding

Caution is advised. It is unknown if pentahydrate is excreted in human milk.

Storage

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

Indications

• Hypokalemia
• Potassium depletion
• Certain types of arrhythmias
• Prevention of hypokalemia in patients receiving diuretics

Dosage

Children: Refer to established guidelines or consult the BNF for Children for specific dosing recommendations.

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

Mechanism of action

Potassium ions play a crucial role in cellular physiology. They are essential for maintaining the resting membrane potential of cells and are involved in the generation of action potentials in excitable tissues such as neurons and muscle cells. The influx and efflux of potassium ions across cell membranes are critical for normal cardiac and neuromuscular function.

Pharmacodynamics

Potassium functions as an essential intracellular cation, influencing various physiological processes. It helps regulate heart rhythm, muscle contraction, and nerve impulses. An adequate potassium level is necessary to prevent muscle weakness, paralysis, and arrhythmias. The relationship between potassium levels and these physiological functions is tightly controlled by renal function and dietary intake.

Pharmacokinetics

Potassium is absorbed primarily in the gastrointestinal tract. Following absorption, it is distributed throughout the body's tissues, with approximately 98% of the body's potassium found intracellularly. The kidneys play a critical role in regulating potassium levels by excreting excess potassium in urine. The half-life of potassium in the body can vary significantly based on renal function, dietary intake, and cellular demands.

Pregnancy

There is insufficient data on the safety of pentapotassium during pregnancy. It should only be used if the benefits outweigh the risks.

Breast-feeding

It is not known if pentapotassium is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

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

• 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

Mechanism of action

Selenate acts by being reduced in the body to selenite and subsequently to hydrogen selenide (H2Se), which is the bioactive form of selenium. This reduction process is vital for the incorporation of selenium into selenoproteins, which are important for various biological functions, including antioxidant defense. The selenate reduction pathway involves several enzymes and is linked to amino acid metabolism and the synthesis of selenoamino acids.

Pharmacodynamics

Selenate exhibits its pharmacological effects mainly through its role in the synthesis of selenoproteins, which are crucial for maintaining cellular redox balance and protecting against oxidative stress. These selenoproteins, including glutathione peroxidases and thioredoxin reductases, contribute to the detoxification of reactive oxygen species and the regulation of various metabolic processes.

Pharmacokinetics

Following administration, selenate is absorbed in the gastrointestinal tract, where it undergoes a series of metabolic transformations. It is reduced to selenite and then to hydrogen selenide, which is incorporated into selenoproteins. The bioavailability of selenate can be influenced by dietary factors and the presence of other selenium sources. The elimination half-life and urinary excretion patterns of selenate may vary depending on individual metabolism and selenium status.

Pregnancy

Selenate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether selenate is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Indications

• Fatigue
• Stress relief
• Enhanced physical performance
• Improved cognitive function
• General wellness support

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate pediatric dosing, as it is not universally established.

Adults: Refer to specific product guidelines or consult a healthcare professional for dosage recommendations as they can vary based on formulation and individual needs.

Mechanism of action

Siberian ginseng contains various bioactive compounds, including eleutherosides, that are thought to modulate the immune system and improve the body's response to stress. These compounds may enhance the activities of neurotransmitters and hormones, aiding in the regulation of energy metabolism and promoting a balanced physiological response to stress.

Pharmacodynamics

The pharmacodynamics of Siberian ginseng involves its ability to enhance physical performance, boost mental clarity, and improve resilience against stress. It is believed to exert these effects through modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in the stress response. Additionally, Siberian ginseng may have antioxidant properties that contribute to its protective effects against oxidative stress.

Pharmacokinetics

The pharmacokinetics of Siberian ginseng is not fully characterized, but studies suggest that its active compounds are absorbed in the gastrointestinal tract. The metabolism of these compounds may occur in the liver, and elimination may be through the urine. The onset of action and duration of effects can vary based on individual factors and the specific preparation used.

Pregnancy

There is insufficient reliable information regarding the safety of Siberian ginseng in pregnancy. It is advised to avoid its use.

Breast-feeding

Limited data is available on the use of Siberian ginseng during breastfeeding. Caution is recommended.

Storage

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

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Allergic reactions
• Hypersensitivity reactions
• Gastrointestinal disturbances

Interactions

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Indications

• 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

Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.

Pharmacodynamics

The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities.

Mechanism of action

Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.

Pharmacodynamics

The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities.

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

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

Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It also plays a role in the hepatic biotransformation and detoxification process; it acts as a hydrophilic molecule that is added to other lipophilic toxins or wastes prior to entering biliary excretion. It participates in the detoxification of methylglyoxal, a toxic by-product of metabolism, mediated by glyoxalase enzymes. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is a cofactor of conjugation and reduction reactions that are catalyzed by glutathione S-transferase enzymes expressed in the cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.

Mechanism of action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacodynamics

Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.

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

Serum and tissue lycopene levels have been inversely related to the risk of lung and prostate cancers. Lycopene functions as a very potent antioxidant, and it can trap singlet oxygen and reduce mutagenesis in the Ames test. Lycopene at physiological concentrations can inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression. Studies using human and animal cells identified connexin 43, a gene whose expression is upregulated by lycopene and which allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors and its restoration or upregulation is associated with decreased proliferation. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibits a synergistic effect on cell proliferation and differentiation, and an additive effect on cell cycle progression in the HL-60 promyelocytic leukemia cell line, suggesting some interaction at a nuclear or subcellular level.

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

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

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.