Calcipus Oral Solution (Each ml contains Calcium Chloride 80mg/ Mangnesium Sulphate 17mg/Zinc Chloride 4.7mg/Copper Sulphate 1.8mg/Magnesium Sulphate 3.7mg)

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

• Magnesium deficiency
• Cardiac arrhythmias
• Eclampsia and pre-eclampsia
• Migraine prophylaxis
• Muscle cramps
• Torsades de pointes

Dosage

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

Adults: Refer to clinical guidelines for specific dosing, as it can vary based on the condition being treated and the form of magnesium used.

Mechanism of action

Magnesium acts primarily as a cofactor for enzymatic reactions, particularly those involving ATP, the energy currency of the cell. It helps stabilize cell membranes and contributes to the regulation of ion channels, including sodium and potassium channels. This stabilization is crucial for maintaining normal neuromuscular function and cardiac rhythm. Additionally, magnesium's role in controlling calcium levels within cells also contributes to its anti-inflammatory and neuroprotective effects.

Pharmacodynamics

Magnesium has a calming effect on the nervous system, which can help alleviate symptoms of anxiety and muscle spasms. It is involved in the regulation of neurotransmitters and neuromuscular transmission. The mineral is also important for glucose metabolism and blood pressure regulation. In high doses, magnesium can produce a laxative effect by inhibiting water absorption in the intestines, leading to increased stool liquidity.

Pharmacokinetics

Magnesium is absorbed in the gastrointestinal tract, with bioavailability varying based on the form of magnesium taken and the presence of food. The kidneys play a vital role in regulating magnesium levels, with excess magnesium being excreted in urine. Plasma half-life for magnesium is approximately 27 hours in healthy adults, but this can be significantly altered in individuals with renal impairment. Distribution occurs primarily in bones, muscles, and soft tissues.

Contra-indications

• Severe renal impairment
• Hypermagnesemia
• Heart block

Adverse effects

• Diarrhea
• Nausea
• Abdominal cramping
• Flushing
• Hypotension
• Respiratory depression

Interactions

• Calcium channel blockers may have additive effects leading to hypotension
• Magnesium can interfere with the absorption of certain antibiotics, such as tetracyclines and fluoroquinolones
• Diuretics (particularly loop diuretics) may affect magnesium levels

Precautions

• Use with caution in patients with renal impairment
• Monitor serum magnesium levels in patients receiving high doses or prolonged therapy
• Caution in patients with cardiovascular disease

Pregnancy

Magnesium is generally considered safe during pregnancy, but high doses should be avoided unless prescribed.

Breast-feeding

Magnesium is excreted in breast milk but is considered safe for use during breastfeeding.

Storage

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

Formulations

• Oral supplements (magnesium oxide, magnesium citrate, magnesium chloride)
• Intravenous magnesium sulfate

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.