PHARMACODYNAMICS Copper is an essential mineral that plays a key role in many physiological processes, including angiogenesis, skin generation and expression and stabilization of skin proteins. Copper is found naturally in many food sources including meats, vegetables, and grains. Copper has potent biocidal properties and is used to eliminate bacteria, viruses and parasites [L1828], [L1839].; ; Copper is one of the nine essential minerals for humans, as it plays an imperative role in various physiological pathways in basically all human tissue, as well as in the health of the dermis and epidermis [L1828].; ; In addition to the above, copper is essential in wound healing, as it promotes angiogenesis and skin extracellular matrix formation and stabilization [L1828].

INDICATION Elemental use in copper deficiency [L1823]; ; Copper and copper containing compounds are broadly used in medical practice. Metallic copper is used already for many years in dental fillings and in copper intrauterine devices (IUD) for reversible contraception. Ointments containing copper, which release copper ions that are absorbed by the skin in the management of cramps, disturbances of renal function, peripheral, venous hypostatic circulatory disturbances, rheumatic disease and swelling associated with trauma. There are also cosmetic facial creams containing copper as their main active ingredient [L1828].

ROE This drug is 80% eliminated via the liver in bile. Minimal excretion by the kidney [L1823].; Metabolism studies show that persons with daily intakes of 2-5 mg of copper per day absorbed 0.6 to 1.6 mg (32%), excreted 0.5 to 1.3 mg in the bile, passed 0.1 to 0.3 mg directly into the bowel, and excreted 0.01 to 0.06 mg in the urine. As the data indicate, urinary excretion plays a negligible role in copper clearance, and the main route of excretion is in the bile. Other nonsignificant excretory routes include saliva, sweat, menstrual flow, and excretion into the intestine from the blood [L1838].

ABSORPTION Primarily absorbed in the small intestine [L1823].; ; Based on studies with radioactive isotopes of copper, most copper is absorbed from the stomach; and duodenum of the gastrointestinal tract. ; ; Maximum blood copper levels are observed within 1 to 3 hours following oral administration, and about 50 percent of ingested copper was absorbed. Copper absorption is proposed to occur by two mechanisms, one energy- dependent and the other enzymatic. Factors that can interfere with copper absorption include competition for binding sites with zinc, interactions with molybdenum and sulfates, chelation with phytates, and inhibition by ascorbic acid (vitamin C) [L1838].; ; Copper absorbed from the gastrointestinal tract is transported rapidly to blood serum and deposited in the liver bound to metallothionein [L1838].; ; From 20 to 60% of the dietary copper is absorbed [L1819].

TOXICITY Acute oral toxicity (LD50): 300 mg/kg in rats [MSDS].; ; Copper sulfate ingestion (accidental or deliberate) is a rare form of poisoning usually limited to the Indian subcontinent. Though the rates are on the decline, it is essential that physicians are aware of its lethal complications and management strategies. The main complications of copper sulfate ingestion include intravascular hemolysis, methemoglobinaemia, acute kidney injury, and rhabdomyolysis [L1827].; ; Severe gastrointestinal effects may occur with acute overdosage. In extreme or long-term overdosage, symptoms may be similar to those of Wilson's disease, a disease in which the liver does not filter copper adequately and copper accumulates in the liver, brain, eyes, and other organs. Gradually, high copper levels may cause life-threatening organ damage [L1823].; ; ; Ingestion of more than 15 mg of copper has been reported to be toxic to humans. In a survey of human clinical case studies, 5.3 mg/day was the lowest oral dose at which local gastrointestinal irritation was seen. Ingestion of gram quantities of copper sulfate resulted in death by suicide, whereas less severe effects were reported from estimated copper doses of 40 to 50 mg from ingestion of carbonated beverages in contact with copper containers. Limited data are available on the chronic toxicity of copper. The hazard from dietary intakes of up to 5 mg/day appears to be low [L1838].; ; Treatment of cupric sulfate toxicity is symptomatic and may involve the use of a chelating agent (e.g. penicillamine, trientine and zinc) to remove any excessive metal that has been absorbed. In addition, dialysis may be useful [L1821, L1823].