How Do Copper Chelators Work?

Copper chelators are a class of drugs used to treat an inherited disorder known as “Wilson’s disease,” a rare genetic metabolic disorder that causes an excess accumulation of copper in some parts of the body, particularly in the liver. These excess amounts of copper damage the organs which are affected. The only drug belonging to this class is "trientine," a chelating agent used to remove toxic metals from the body (such as lead, mercury, or copper). Copper chelators work by reducing the toxic levels of copper in the body and preventing re-accumulation of copper.

Copper plays a key role in the development of healthy nerves, bones, collagen, and skin pigment melanin. Normally, copper is absorbed from the food, and the excess amount is excreted through a substance produced in the liver (bile). But in people with Wilson's disease (affecting approximately 1 in 30,000 people worldwide), copper is not eliminated properly and thus accumulated, possibly to a life-threatening level.

Wilson's disease is present at birth, but signs and symptoms do not appear until the copper builds up in the brain, liver, or other organs. It is characterized by signs and symptoms such as:

• Abdominal pain
• Lack of appetite
• Fatigue (feeling of tiredness or lack of energy)
• Yellowing of the skin and the whites of the eye (jaundice)
• Golden-brown eye discoloration (Kayser-Fleischer rings)
• Fluid buildup in the legs or abdomen
• Problems with speech, swallowing, or physical coordination
• Uncontrolled movements or muscle stiffness

Copper chelators are administered orally on an empty stomach at least one hour before meals or two hours after meals, typically two to four times daily.

Copper chelators work in the following ways:

• In healthy conditions, the liver is responsible for filtering out the excess amount of copper and excreting it through urine; however, in Wilson’s disease, the liver cannot function properly, thus leading to accumulation of excess amount of copper in the body.
• They tightly bind to the excess amount of copper to form complexes that facilitate the systemic elimination of copper through urine.
• They may also act as an antioxidant, as they suppress the copper-mediated oxidative stress, but do not cause systemic copper deficiency even after prolonged use.
• In addition, they decrease intestinal copper absorption by 80%.

Copper chelators are used to treat Wilson's disease in patients intolerant of penicillamine.

Some of the common side effects include:

• Weakness/tiredness
• Abdominal pain
• Loss of taste
• Heartburn (an uncomfortable burning feeling in the chest)
• Anorexia (lack or loss of appetite)
• Pale skin

Other rare side effects include:

• Gastritis (inflammation of the stomach lining)
• Dystonia (a state of abnormal muscle tone, resulting in muscular spasm and abnormal posture)
• Iron deficiency
• Muscular spasm (muscle cramps)
• Aplastic anemia (a condition that occurs when the body stops producing enough new blood cells)
• Rash/thickening and fissuring of the skin
• Aphthoid ulcer (painful punched-out sore on oral or genital mucous membranes)
• Lupus-like eruption (a butterfly-shaped rash across the cheeks and bridge of the nose)
• Myasthenia gravis (a chronic autoimmune, neuromuscular disease that causes weakness in the skeletal muscles, which worsens after periods of activity and improves after periods of rest)
• Systemic lupus erythematosus (a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of copper chelators include:

• Clovique
• Syprine
• Trientine