Heavy metals: Lead, arsenic, mercury, cadmium, radioactive metals.

Heavy metal intoxication: Exposure via environment (water, food, utensils, cookware), occupational settings (mining, industry), pollution (fossil fuels, leaded gasoline). Metals exert toxicity by combining with reactive groups (ligands) essential for physiological functions: oxygen (-OH, -COO-), sulfur (-SH), nitrogen (-NH). Chelating agents are designed to compete for these metals, prevent/reverse toxicity, enhance excretion.

Chelating: Formation of complexes between chelating agents and metal ions, preventing metal binding to body ligands.

Ideal chelator properties: Water solubility, resistance to biotransformation, reaches storage sites, forms nontoxic complexes, active at body pH, readily excreted, low affinity for Ca2+ to avoid hypocalcemia. Most important: greater affinity for toxic metal than endogenous ligands.

Heavy metal antagonists (chelators): EDTA, Edetate disodium, Edetate calcium disodium, Dimercaprol, Succimer, Deferoxamine, Penicillamine, Trientine.

Used historically as therapeutic/poison. Now for topical diseases (African trypanosomiasis).

Sources: Soil, water, air, smelting byproducts, mineral springs, coal combustion, herbicides/pesticides, fruits/vegetables, tube well water, poultry feed.

Chemical forms: Elemental, trivalent (As3+), pentavalent (As5+), organic arsenicals.

Toxicity order: Arsine (AsH3) > Trivalent > Pentavalent > Organic.

Inorganic: Arsenic acid, potassium/lead arsenate, arsine gas, arsenic oxide.

Organic: Arsphenamine, sodium arsenilate (excreted faster).

• Pentavalent: Interferes with mitochondrial oxidative phosphorylation via arsenolysis (competes with phosphate in ATP formation → unstable arsenate ester hydrolyzed).
• Trivalent: Sulfhydryl reagents; inhibit enzymes by reacting with -SH groups (e.g., pyruvate dehydrogenase via lipoic acid).

Absorption: Depends on solubility. Trivalent/pentavalent forms well absorbed (80–90%).

Distribution: Stored in liver, kidney, heart, lung. High in hair/nails (keratin), bone/teeth (similar to phosphorus). Crosses placenta.

Metabolism: Pentavalent reduced to trivalent (via GSH oxidation). Trivalent methylated to methyl/dimethyl arsenite → eliminated.

Excretion: Urine (main), feces, sweat, milk, hair, skin, lungs. Urinary t1/2: 3–5 days.

• CVS: Vasodilation → edema; capillary damage → hypotension; chronic → peripheral vascular disease ("black feet disease"), myocardial damage.
• Kidney: Glomerular/tubular damage → proteinuria, hematuria, casts, oliguria, necrosis.
• Skin: Hyperpigmentation, hyperkeratosis (palms/soles), "milk and roses" complexion.
• Nervous system: Encephalopathy, peripheral neuropathy, diminished reflexes, muscular atrophy.
• Blood: Bone marrow suppression → anemia, leukopenia, eosinophilia, anisocytosis (impaired folate absorption).
• Liver: Fatty infiltration, necrosis, cirrhosis.
• GIT: Abdominal cramping, diarrhea, hemorrhagic gastroenteritis, hematemesis, bloody feces, stomatitis.
• Carcinogenesis: Skin, lung, bladder, kidney, liver cancers.
• Others: Diabetes, goiter, hepatomegaly, respiratory dysfunction.

Acute poisoning: GI discomfort, burning lips, throat constriction, dysphagia, gastric pain, projectile vomiting, severe diarrhea, oliguria/proteinuria/hematuria/anuria, muscle cramps, thirst, shock, convulsions, coma. Death within hour if untreated.

Chronic poisoning: Muscle weakness/aching, skin pigmentation, hyperkeratosis, edema, garlic breath/sweat, salivation/sweating, stomatitis, sore throat, itching, numbness, lacrimation, dermatitis, alopecia, hepatomegaly/jaundice, cirrhosis, renal dysfunction, encephalopathy, peripheral neuritis, hematological damage.

A. Preventive measures:

• Prevent further absorption: emesis (apomorphine), gastric lavage, activated charcoal, cathartics.
• Remove from exposure (inhalation/skin/eye): irrigation 15 min.
• Manage hypovolemic shock: fluid replacement, pressors (dopamine).

B. Main treatment (Chelation therapy):

• Start with Dimercaprol (3–4 mg/kg IM every 4–12h until symptoms subside).
• Then oral Penicillamine (max 2 g/day for 4 days). Repeat if symptoms recur.
• For chronic exposure, Penicillamine alone often sufficient.
• Monitor urinary arsenic levels.
• Dialysis if severe nephrotoxicity.