SN5 SHORT NOTE 5M ★ High-yield

Describe the chelating agents and the management of heavy metal poisoning.

Pharmacology · 2nd Professional — Para-Clinical

Principles of Chelation

A chelating agent is a compound that forms a stable, non-toxic, water-soluble complex with a metal ion, which is then excreted — the term comes from the Greek for a crab's claw.

A good chelator has high affinity for the toxic metal and low affinity for essential ones (calcium, zinc, iron); is water-soluble and excreted renally; is stable at physiological pH; and does not redistribute the metal into the brain
Chelation is not without cost — essential trace metals are removed alongside, and supplementation may be needed

The Chelating Agents

Agent	Metals chelated	Notes
Dimercaprol (BAL, British Anti-Lewisite)	Arsenic, mercury, gold, lead (with EDTA)	Developed as an antidote to the arsenical war gas lewisite. Given deep intramuscularly in peanut oil, which is painful; causes hypertension, tachycardia, nausea and fever. Contraindicated in iron, cadmium and selenium poisoning, where the complex is more toxic than the metal
Calcium disodium EDTA	Lead (the classical agent)	The calcium salt must be used — disodium EDTA alone chelates the patient’s own calcium and causes fatal hypocalcaemic tetany. Nephrotoxic; does not enter cells or the CNS well
DMSA (succimer)	Lead, arsenic, mercury	Orally active, far less toxic and more selective than the older agents; now first-line for childhood lead poisoning
Penicillamine	Copper (WILSON disease), lead, mercury, gold	Oral; causes rash, proteinuria and nephrotic syndrome, marrow suppression, a lupus-like syndrome, and pyridoxine deficiency (supplementation needed). Trientine is the better-tolerated alternative
Desferrioxamine	Iron, aluminium	Parenteral; the antidote in acute iron poisoning and in transfusional overload; produces a characteristic "vin rose" urine
Deferasirox, deferiprone	Iron	Orally active, which transformed adherence and survival in thalassaemia. Deferasirox causes renal and hepatic impairment and gastrointestinal haemorrhage; deferiprone causes agranulocytosis requiring blood count monitoring, but reaches cardiac iron better

CLINICAL PEARL

Calcium disodium EDTA and disodium EDTA differ by one word and one death. The disodium salt has no calcium bound to it, so on infusion it strips calcium from the plasma and causes fatal hypocalcaemic tetany and arrhythmia. Only the calcium disodium salt — already carrying calcium, which lead displaces — is safe. Deaths from this confusion are documented, and it is the reason the full name must always be written out.

Lead Poisoning

Sources in India — contaminated traditional and ayurvedic medicines, surma and kajal, lead-glazed pottery, battery recycling, paint in older buildings, and industrial exposure
Features in adults — abdominal colic, constipation, a blue lead line on the gums, wrist and foot drop from motor neuropathy, anaemia with basophilic stippling, hypertension and nephropathy
Features in children — encephalopathy, seizures, and above all impaired cognitive development, which is irreversible; there is no threshold below which lead is known to be safe
Mechanism — lead inhibits delta-aminolevulinic acid dehydratase and ferrochelatase, blocking haem synthesis, and interferes with calcium-dependent processes throughout the nervous system
Treatment — remove the source first (chelation while exposure continues is futile); DMSA orally for moderate poisoning; dimercaprol with calcium disodium EDTA for encephalopathy or very high levels, with dimercaprol given first to avoid redistributing lead into the brain

Other Heavy Metals

Arsenic — from contaminated groundwater, a major public health problem in West Bengal and Bihar. Causes hyperpigmentation, palmar and plantar keratoses, "raindrop" pigmentation, peripheral neuropathy, and cancers of skin, bladder and lung. Acute poisoning causes severe gastroenteritis with a garlic odour. Treated with DMSA or dimercaprol, and prevented by safe water supply
Mercury — elemental (vapour, causing pneumonitis and tremor), inorganic (corrosive, renal failure), and organic methylmercury from fish, which is neurotoxic and teratogenic (Minamata disease). Chelated with DMSA or penicillamine; dimercaprol is avoided in organic mercury poisoning, as it redistributes mercury into the brain
Copper — WILSON disease: an autosomal recessive defect in biliary copper excretion causing hepatic and neurological disease with KAYSER-fleischer rings. Treated with penicillamine or trientine, and zinc, which induces intestinal metallothionein and blocks absorption; a low-copper diet is advised

Applied Aspects

Remove the source before chelating; continued exposure makes chelation pointless and repeated courses harmful
Ask about traditional and ayurvedic medicines in any unexplained anaemia, neuropathy or abdominal pain; heavy metal contamination of such preparations is well documented in India and patients do not regard them as drugs
Screen exposed children and workers; lead affects cognition at levels that cause no symptoms at all, and the damage cannot be undone
Never write "EDTA" without qualifying it
Arsenic in groundwater requires an engineering solution — deep tube wells, filtration and testing — not a pharmacological one; chelation treats the patient while the village remains exposed
Consider Wilson disease in any young person with unexplained liver disease or a movement disorder; it is treatable, and fatal if missed

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