ADDITRACE

Indications

• Impaired glucose tolerance
• Type 2 diabetes mellitus
• Metabolic syndrome
• Hyperlipidemia

Dosage

Children: Refer to specific product guidelines or clinical literature for dosing recommendations, as they may vary based on the formulation used.

Adults: Refer to specific product guidelines or clinical literature for dosing recommendations, as they may vary based on the formulation used.

Mechanism of action

Chromium enhances the action of insulin, a hormone critical for glucose metabolism. It is believed to do this by facilitating the translocation of glucose transporters to the cell membrane, thereby increasing glucose uptake by cells. Additionally, chromium may influence lipid metabolism and improve lipid profiles.

Pharmacodynamics

Chromium is involved in the metabolism of macronutrients, particularly in the modulation of insulin action. It helps to maintain normal blood glucose levels and may also influence lipid metabolism by promoting the utilization of fats and decreasing fat storage. Its effects are dose-dependent and may vary based on the form of chromium used.

Pharmacokinetics

Chromium is absorbed in the gastrointestinal tract, with absorption rates generally low and influenced by dietary factors. It is distributed throughout the body, primarily in the liver, spleen, and bones. The elimination half-life of chromium is not well defined, but it is primarily excreted through urine. Chronic intake may lead to bioaccumulation in tissues.

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Local irritation at injection site
• Anaphylaxis (rare)

Precautions

• Use with caution in patients with hypersensitivity to chromic compounds
• Monitor for potential allergic reactions during administration

Pregnancy

Safety in pregnancy has not been established; use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

Caution is advised; limited data on excretion in breast milk.

Storage

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

Formulations

• Chromic chloride solution for parenteral administration
• Chromic oxide
• Chromate salts

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

• Iron deficiency anemia
• Chronic blood loss
• Nutritional iron deficiency
• Pregnancy-related anemia

Dosage

Children: Refer to the BNF for Children for specific dosing information as it may vary based on the formulation and clinical context.

Adults: Refer to the BNF for specific dosing information as it may vary based on the formulation and clinical context.

Mechanism of action

Ferric ions participate in various biological processes, including oxygen transport and electron transfer. They facilitate the formation of hemoglobin in red blood cells, allowing for efficient oxygen delivery throughout the body. Ferric compounds can also promote the absorption of iron from the gastrointestinal tract by providing a more bioavailable form of iron.

Pharmacodynamics

Ferric compounds exhibit their effects primarily through the restoration of iron levels in the body. This leads to improved synthesis of hemoglobin and overall enhancement of oxygen-carrying capacity. The pharmacological action is dose-dependent, with higher doses leading to more pronounced effects on hemoglobin levels and erythropoiesis. Additionally, ferric ions can influence various metabolic pathways involved in cellular respiration and energy production.

Pharmacokinetics

Ferric is absorbed in the gastrointestinal tract, with absorption rates influenced by dietary factors and the presence of other substances in the gut. Once absorbed, ferric ions are transported in the bloodstream bound to transferrin, a transport protein. The body regulates iron levels primarily through absorption rather than excretion, and excess iron can be stored in the liver, spleen, and bone marrow. The elimination of ferric compounds is generally slow, as they are incorporated into various biological systems or stored for future use.

Contra-indications

• Hypersensitivity to ferric compounds
• Iron overload conditions such as haemochromatosis or haemosiderosis
• Chronic liver disease
• Active peptic ulcer disease

Adverse effects

• Gastrointestinal disturbances including nausea, vomiting, and constipation
• Diarrhea
• Abdominal pain
• Black stools
• Allergic reactions including rashes and anaphylaxis
• Staining of teeth (with oral formulations)

Interactions

• Antacids may reduce the absorption of oral ferric preparations
• Tetracyclines and quinolone antibiotics may have reduced absorption when taken with iron
• Ascorbic acid may enhance the absorption of iron

Precautions

• Caution in patients with a history of gastrointestinal disease
• Monitor for signs of iron overload in patients receiving repeated doses
• Use with caution in patients with renal impairment

Pregnancy

Ferric compounds are generally considered safe in pregnancy when used as directed to treat iron deficiency, but should be used under medical supervision.

Breast-feeding

Ferric compounds are excreted in breast milk in small amounts, usually considered safe but should be used under medical supervision.

Storage

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

Formulations

• Oral tablets
• Oral solution
• Intravenous injection

Indications

• Prevention of dental caries
• Treatment of dental hypersensitivity
• Topical application for high caries risk patients

Dosage

Children: Refer to the BNF for Children for specific paediatric dosage recommendations, which are typically based on age and dental health needs.

Adults: Refer to the BNF for specific adult dosage recommendations, which may vary based on the formulation and indication.

Mechanism of action

Fluoride acts primarily by enhancing the mineralization process of the tooth enamel through the formation of fluorapatite, which is more resistant to acid dissolution than hydroxyapatite. It also inhibits the activity of specific enzymes in bacteria that contribute to acid production, thereby reducing the overall cariogenic potential of dental plaque.

Pharmacodynamics

Fluoride exhibits a dose-dependent effect on dental health, with low concentrations promoting enamel remineralization and higher concentrations potentially toxic to bacteria. Its effectiveness is attributed to its ability to integrate into the crystalline structure of teeth, leading to improved resistance to acid attacks. Additionally, fluoride can modulate the metabolism of oral bacteria, reducing their ability to produce acid from fermentable carbohydrates.

Pharmacokinetics

Fluoride is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after ingestion. It is distributed throughout the body, with significant accumulation in bones and teeth. The elimination half-life varies, but fluoride is primarily excreted unchanged via the kidneys. The clearance rate can be influenced by renal function as well as dietary factors.

Pregnancy

Fluoride is generally considered safe during pregnancy when used in appropriate doses for dental health. However, excessive intake should be avoided.

Breast-feeding

Fluoride is excreted in breast milk in small amounts. It is generally regarded as safe for breastfeeding mothers when used appropriately.

Storage

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

Indications

• Iodine deficiency
• Hypothyroidism
• Goiter
• Thyroiditis

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Iodide functions as a substrate for the synthesis of thyroid hormones. It undergoes metabolism through various pathways, including thyroid hormone metabolism via conjugation and degradation, deiodination, and biosynthesis. In the thyroid gland, iodide is actively transported into cells where it is oxidized to iodine, which then combines with the amino acid tyrosine to form T3 and T4, essential hormones for metabolic regulation.

Pharmacodynamics

Iodide is crucial for maintaining thyroid hormone levels in the body. Adequate iodide levels are necessary to prevent hypothyroidism and associated conditions such as goiter. The pharmacodynamic effects include modulation of metabolic processes, enhancement of growth and development, and regulation of energy expenditure. Insufficient iodide can lead to decreased thyroid hormone production and subsequent metabolic disturbances.

Pharmacokinetics

Iodide is absorbed from the gastrointestinal tract and is distributed throughout the body, particularly accumulating in the thyroid gland. The half-life of iodide in the serum is approximately 10-20 days, depending on dietary intake and physiological status. It is excreted primarily through the kidneys. The bioavailability of iodide can be influenced by various factors, including the presence of certain food components and the overall dietary iodide intake.

Pregnancy

Iodide is generally considered safe during pregnancy when used in appropriate doses, as it is essential for fetal thyroid function.

Breast-feeding

Iodide is excreted in breast milk, but it is usually safe in normal dietary amounts.

Storage

Store in a cool, dry place, protected 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

• Molybdenum deficiency
• Supportive therapy in conditions related to sulfite metabolism disorders

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Molybdate functions primarily as a cofactor for enzymes involved in the metabolism of sulfur, nitrogen, and carbon. It facilitates the activity of enzymes such as sulfite oxidase, which converts sulfite to sulfate, and xanthine oxidase, which is involved in purine metabolism. The presence of molybdenum in these enzymatic reactions is vital for their catalytic activities, highlighting its importance in biochemical pathways.

Pharmacodynamics

As a trace element, molybdate influences various metabolic pathways. It is essential for the proper functioning of enzymes that catalyze critical reactions in amino acid and nucleotide metabolism. The pharmacodynamic effects of molybdate are primarily related to its role in enzyme activation and its contribution to maintaining normal physiological functions, particularly in detoxifying harmful substances like sulfites.

Pharmacokinetics

Molybdate is absorbed in the gastrointestinal tract, with its bioavailability influenced by dietary sources and the presence of competing minerals. It is distributed throughout the body, incorporating into tissues where molybdenum-dependent enzymes are active. The elimination of molybdate occurs primarily through renal excretion, with minimal accumulation in the body under normal dietary conditions.

Pregnancy

Molybdate should be used during pregnancy only if clearly needed.

Breast-feeding

Molybdate is excreted in breast milk, caution is advised.

Storage

Store in a tightly closed container, protected from light and moisture.

Formulations

• Molybdate salts

Indications

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

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Formulations

• Sodium selenite

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.