HB GLOW LIQUID

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 B2 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Metabolic diseases
• Cystathioninuria
• Homocystinuria
• Wilson's disease
• Prevention of penicillamine-induced neuropathy

Mechanism of action

Riboflavin acts as a precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential coenzymes in various enzymatic reactions. It binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase, facilitating the production of FMN and FAD. These coenzymes are critical for normal tissue respiration and energy metabolism, influencing hydrogen transport in oxidative enzyme systems such as cytochrome C reductase and succinic dehydrogenase. Moreover, riboflavin contributes to the antioxidant activity by aiding in the production of reduced glutathione, a key antioxidant in the body.

Pharmacodynamics

Riboflavin is an easily absorbed, water-soluble micronutrient that supports energy production by assisting in the metabolism of fats, carbohydrates, and proteins. It is vital for red blood cell formation, antibody production, and regulating growth and reproduction. The vitamin plays a significant role in maintaining healthy skin, nails, and hair, as well as supporting thyroid activity. Riboflavin also has therapeutic implications in preventing or treating various eye disorders, including cataracts.

Pharmacokinetics

Riboflavin is rapidly absorbed in the gastrointestinal tract, with its bioavailability influenced by dietary intake. It is primarily excreted through urine, with excess intake leading to bright yellow urine, which is a harmless side effect. The vitamin does not accumulate in the body, necessitating regular dietary intake to maintain adequate levels.

Adverse effects

• Urine discolouration
• Peripheral neuritis

Precautions

• With intravenous use, risk of cardiovascular collapse; resuscitation facilities must be available and monitor closely.

Pregnancy

Crosses the placenta but no adverse effects reported; information at high doses limited.

Breast-feeding

Present in breast milk but no adverse effects reported; information at high doses limited.

Storage

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

Formulations

• 100 mg modified-release tablets
• 50 mg capsules
• 100 mg capsules
• 100 mg tablets
• Oral solution

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

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

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.

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

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

Interactions

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Tablets
• Oral solutions
• Injectable forms

Indications

• Rheumatoid arthritis
• Allergic diseases
• Peptic ulcers
• Anemia

Dosage

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

Adults: Refer to BNF for specific dosing information based on condition and individual patient factors.

Mechanism of action

The specific actions of supplemental L-histidine are not completely understood, but it is known that L-histidine serves as a precursor for histamine through the process of decarboxylation. Histamine is associated with immunomodulatory and antioxidant effects, which may help in conditions such as rheumatoid arthritis by activating suppressor T cells and reducing reactive oxygen species production in immune cells. Additionally, L-histidine can chelate metals that participate in oxidative reactions, potentially protecting tissues from oxidative damage.

Pharmacodynamics

Histidine is essential for the synthesis of proteins and is found in high concentrations in hemoglobin. Its metabolites, including histamine, play significant roles in immune response regulation and oxidative stress management. A deficiency in histidine can lead to various health issues, including impaired hearing and reduced immune function.

Pharmacokinetics

Histidine is readily absorbed in the intestines and distributed throughout the body. It undergoes metabolic conversion primarily in the liver, where it is transformed into histamine and other metabolites. The elimination of histidine occurs through various metabolic pathways, and it is excreted in urine primarily as metabolites.

Pregnancy

Histidine is generally regarded as safe during pregnancy when consumed in food. However, the safety of high-dose supplementation has not been established.

Breast-feeding

Histidine is considered safe during breastfeeding in dietary amounts. The effects of high-dose supplementation are not well studied.

Storage

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

Formulations

• L-histidine capsules
• L-histidine powder

Indications

• Herpes simplex virus infections
• Lysine deficiency

Dosage

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

Adults: Refer to the BNF for specific dosage recommendations.

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Gastrointestinal upset
• Diarrhea
• Nausea
• Abdominal pain

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Oral tablet
• Oral capsule
• Powder for oral solution

Indications

• Smoking cessation
• Management of withdrawal symptoms from tobacco dependence

Dosage

Adults: Refer to BNF for specific

Mechanism of action

Nicotine acts as an agonist at nicotinic acetylcholine receptors, specifically binding to receptors in dopaminergic neurons within the cortico-limbic pathways of the brain. This binding results in the opening of ion channels, allowing the influx of sodium, calcium, and potassium ions, leading to depolarization. The depolarization activates voltage-gated calcium channels, facilitating increased calcium entry into the axon terminal, which subsequently promotes the release of dopamine. This release of dopamine is responsible for the euphoric and addictive effects associated with nicotine. Additionally, nicotine activates nicotinic receptors in the adrenal medulla, resulting in epinephrine release, which contributes to increased blood pressure, heart rate, and blood glucose levels.

Pharmacodynamics

Upon administration, nicotine binds selectively to nicotinic-cholinergic receptors located in autonomic ganglia, the adrenal medulla, neuromuscular junctions, and the central nervous system. It exhibits stimulant effects through activation of the locus ceruleus and induces rewarding effects in the limbic system. Its pharmacological actions are complex, characterized by the release of neurotransmitters such as acetylcholine, norepinephrine, dopamine, and others, leading to increased peripheral vasoconstriction, tachycardia, and elevated blood pressure. Nicotine is recognized for its high potential for addiction.

Pharmacokinetics

Nicotine is rapidly absorbed when delivered through various routes including smoking, transdermal patches, or inhalation. It undergoes extensive hepatic metabolism primarily via the cytochrome P450 system, with a half-life of approximately 1 to 2 hours. The metabolites are primarily excreted through urine. Due to its lipophilic nature, nicotine crosses biological membranes easily, including the blood-brain barrier, leading to its central nervous system effects.

Contra-indications

• Hypersensitivity to nicotine or any of the excipients
• Severe cardiovascular disease
• Pregnancy (in non-replacement therapies)

Adverse effects

• Nausea
• Dizziness
• Headaches
• Tachycardia
• Increased blood pressure
• Insomnia
• Anxiety
• Irritability
• Withdrawal symptoms

Interactions

• May interact with other medications affecting cardiovascular function
• CYP1A2 inhibitors may increase nicotine levels
• CYP1A2 inducers may decrease nicotine levels

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor for signs of cardiovascular instability
• Consider potential for nicotine dependence

Pregnancy

Nicotine is contraindicated in pregnancy, as it may harm fetal development and increase the risk of complications.

Breast-feeding

Nicotine is excreted in breast milk, and breastfeeding while using nicotine replacement therapy should be approached with caution.

Storage

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

Formulations

• Transdermal patches
• Gums
• Lozenges
• Inhalers
• Nasal sprays

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

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Allergic reactions
• Hypersensitivity reactions
• Gastrointestinal disturbances

Interactions

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Mechanism of action

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

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

Pharmacodynamics

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

Mechanism of action

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

Pharmacodynamics

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

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

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

Pharmacodynamics

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

Mechanism of action

Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints. L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis. This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

Pharmacodynamics

Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.

Mechanism of action

Proteins of the herpes simplex virus are rich in L-arginine, and tissue culture studies indicate an enhancing effect on viral replication when the amino acid ratio of L-arginine to lysine is high in the tissue culture media. When the ratio of L-lysine to L-arginine is high, viral replication and the cytopathogenicity of herpes simplex virus have been found to be inhibited. L-lysine may facilitate the absorption of calcium from the small intestine. Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Amino acids/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Amino acids/

Pharmacodynamics

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

Mechanism of action

Nicotine is a stimulant drug that acts as an agonist at nicotinic acetylcholine receptors. These are ionotropic receptors composed up of five homomeric or heteromeric subunits. In the brain, nicotine binds to nicotinic acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways. This causes the channel to open and allow conductance of multiple cations including sodium, calcium, and potassium. This leads to depolarization, which activates voltage-gated calcium channels and allows more calcium to enter the axon terminal. Calcium stimulates vesicle trafficking towards the plasma membrane and the release of dopamine into the synapse. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine. Nicotine also binds to nicotinic acetylcholine receptors on the chromaffin cells in the adrenal medulla. Binding opens the ion channel allowing influx of sodium, causing depolarization of the cell, which activates voltage-gated calcium channels. Calcium triggers the release of epinephrine from intracellular vesicles into the bloodstream, which causes vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar. Nicotine is a ganglionic (nicotinic) cholinergic-receptor agonist. The pharmacologic actions of nicotine are complex and include a variety of effects mediated by stereospecific binding to receptors in autonomic ganglia, the adrenal medulla, the neuromuscular junction, and the brain. The principal pharmacologic effect of small doses of nicotine is initial, transient stimulation of autonomic ganglia; large doses or prolonged neuronal receptor exposure to nicotine results in subsequent persistent depression of receptor activity. Although nicotine has similar dose-related effects at the myoneural (neuromuscular) junction, rapidly developing skeletal muscle paralysis obscures the stimulant phase. The muscle-relaxant properties of nicotine may be mediated through stimulation of Renshaw cells and pulmonary afferent nerves, which results in inhibition of skeletal muscle motor activity; such relaxant effects may contribute to the behavior-reinforcing effects of the drug. Small doses of nicotine directly stimulate sympathetic ganglia and facilitate neurotransmission; however, large doses produce initial ganglionic stimulation, which is quickly followed by inhibition of neurotransmission.

Pharmacodynamics

Nicotine, the primary alkaloid in tobacco products binds stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at the locus ceruleus and a reward effect in the limbic system. Itranvenous administration of nicotine causes release of acetylcholine, norepinephrine, dopamine, serotonine, vasopressin, beta-endorphin and ACTH. Nicotine is a highly addictive substance. Nicotine also induces peripheral vasoconstriction, tachycardia and elevated blood pressure. Nicotine inhalers and patches are used to treat smoking withdrawl syndrome. Nicotine is classified as a stimulant of autonomic ganglia.

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.