DEFINITION
These are the chemical agents or drugs with two or more than two electronegative group that can form stable covalent coordinate bonds with cationic metal atoms, i.e. they are the drug which provide “ligand” to the metallic ion and form a complex (ring) which is stable, non toxic and easily excretable. By this they interfere with normal cell functions which require these ligands. Heavy metals cannot be metabolized in the body.
Chelating agents or heavy metal antagonists bind the heavy metal ions and therefore make them non-toxic. The chemical complex formed is called chelate (chele=claw; in Greek). The process of complex formation is chelation. The complex so formed is water-soluble and is eliminated by the kidneys.
Some important chelating agents are:
- BAL (Dimercaprol): British antilewisite.
- Succimer (Dimercaptosuccinate)
- EDTA (Disodium editate): Ethylene Diamino Tetra Acetic acid
- Diethylene Triamine Penta Acetic Acid, DTPA (Ca-disodium DTPA)
- Desferrioxamine
- Penicillamine deferprone.
Dimercaprol (BAL): British antilewisite: It is colorless oily liquid, given parenterally and developed by the British during World War II as an antidote to lewisite-an arsenical war gas. Hence it is also known as British Antilewisite or BAL. Required in 2 BAL: 1 metal ratio.
Indications
- Poisoning of As (Arsenic), Hg (Mercury), Au (Gold), Bi (Bismuth), Sb (Antimony), etc.
- As an adjuvant to penicillamine in copper poisoning.
- As an adjuvant to calcium disodium EDTA in lead poisoning.
Dose: 5 mg/kg stat followed by 2–3 mg/kg intramuscular every 4 to 8 hourly for 2 days (urine should be alkaline).
Adverse effect
- GIT disturbance like nausea, vomiting, etc
- Hypertension, tachycardia, headache and lacrymation, etc. (managed with antihistaminics).
Dimercaprol succimer (DMSA) and Dimercaprol sulfonate (DMSP): Their advantages over BAL are:
- More polar and therefore confined to extracellular space
- Less cellular toxicity
- Administered orally (effective)
- They are used specifically in the treatment of lead poisoning, specially in children; in arsenic and mercury poisoning, for prevention of renal stone formation in the patients with homozygous cyctinuria.
Calcium disodium edetate (CaNa2 EDTA): It chelates many divalent and trivalent metals like zinc, manganese, iron and lead. It is used in the treatment of lead poisoning. Given parenterally, lead deposits in the bone are mobilised, chelated and excreted through kidneys.
Indications: CaNa2 EDTA is mainly used in the treatment of lead poisoning. It can also be used in zinc, manganese and iron poisoning. Sodium Edetate is used in severe hypercalcemia.
Dose: 1 gm diluted in 200–300 ml of normal saline infused over 1 hours
Adverse effects include:
- Fatigue, fever, myalgia but no tetany
- Nephrotoxicity and dermatitis.
d-Penicillamine: It is a dextro isomer and is prepared by degradation of penicillin but has no antibacterial activity. It chelates copper, mercury, zinc, and lead. It is orally effective.468
Uses
- Treatment of copper, mercury, zinc and lead poisoning.
- Wilson's disease (hepatolenticular degeneration)-copper is deposited in liver and brain causing degeneration.
- Treatment of severe rheumatoid arthritis.
- Treatment of scleroderma
- Cystinuria- promotes excretion of cysteine by forming soluble complexes and prevents formation of cysteine stones.
Doses: 0.5–1 gm/day orally.
Toxicity
- Patients allergic to penicillin may develop anaphylaxis; dermatitis may occur in some.
- On long-term use renal, hematological, dermatological and other toxicities can occur.
- Cutaneous: itching, burning sensation, etc.
Desferrioxamine: It is obtained from (actinomycetes) streptomyces. It has a high affinity for iron, forms stable complexes and removes iron from hemosiderin and ferritin. It does not chelate the iron in hemoglobin and cytochromes. It is given parenterally. It has no affinity for heme iron (Hb).
Side effect: Allergic reaction range from rashes to anaphylaxis (rare), diarrhea, muscle cramps and blurred vision.
Uses
- Acute iron poisoning-desferrioxamine is the drug of choice.
- Chronic iron poisoning-as in thalassemia patients who receive repeated blood transfusion.
- Dose: 0.5 to 1 gm/day intramuscular.
Side effect: Abdominal pain, loose motion and some time ophthalmic side effects.
Deferiprone
- It is an orally active iron chelator
- Indication: Acute iron poisoning
- Side effect: Agranulocytosis