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Heavy Metals Toxicity

People continue to be exposed to heavy metals in the environment. Metals contaminate water and food in some areas. Metals also leach from eating utensils and cookware. The emergence of the industrial age and large-scale mining brought occupational diseases caused by various toxic metals. Metallic constituents of pesticides and even therapeutic agents have been additional sources of hazardous exposure. The burning of fossil fuels containing heavy metals and the increase in industrial applications of metals have made environmental pollution the major source of heavy-metal poisoning.

Heavy Metals Toxicity

Heavy metals exert their toxic effects by combining with one or more reactive groups (ligands) essential for normal physiological functions. Heavy metals, particularly those in the transition series, may react in the body with ligands containing oxygen (-OH, -COO-, - OPO3H-, >CO=), sulfur (-SH,-S-S-), and nitrogen (-NH2 and >NH). The resulting metal complex (or coordination compound) is formed by a coordinate bond in which both electrons are contributed by the ligand.

Through natural occurrence and its industrial use, lead is ubiquitous(existing every where) in the environment. The primary sources of environmental exposure to lead are leaded paint and drinking water; most of the overt toxicity from lead results from environmental and industrial exposures. Occupational exposure to lead has decreased markedly because of appropriate regulations and programs of medical surveillance. Workers in lead smelters have the highest potential for exposure because fumes are generated, and dust containing lead oxide is deposited in their environment. Workers in storage-battery factories face similar risks.

Lead Dietary intake of lead has decreased since the 1940s due largely to
decrease in the use of lead-soldered cans for food and beverages; decrease in the use of lead pipes and lead-soldered joints in water distribution systems; introduction of lead-free gasoline;

public awareness of the hazards of indoor leaded paint

The major routes of absorption of lead are from the GIT and the respiratory system. Adults absorb approximately 10% of ingested lead, whereas children absorb up to 40%. Approximately 90% of inhaled lead particles from ambient air are absorbed. 4

After absorption, about 99% of lead in the bloodstream binds to hemoglobin in erythrocytes. Only 1% to 3% of the circulating blood lead is in the serum available to the tissues. Inorganic lead initially distributes in the soft tissues, particularly the tubular epithelium of the kidney and in the liver. In time, lead is redistributed and deposited in bone, teeth, and hair. About 95% of the body burden of lead eventually is found in bone. Only small quantities of inorganic lead accumulate in the brain, mostly in gray matter and the basal ganglia. Iron and Ca2+ may compete with lead transport.

Urinary excretion is a more important route of excretion in humans. The concentration of lead in urine is directly proportional to that in plasma, but because most lead in blood is in the erythrocytes, only a small quantity of lead is filtered. Lead also is excreted in milk and sweat and is deposited in hair and nails. Placental transfer of lead also occurs. The half-life of lead in blood is 1 to 2 months, and a steady state thus is achieved in about 6 months.


After establishment of a steady state early in human life, the daily intake of lead normally approximates the output, and concentrations of lead in soft tissues are relatively constant. However, the concentration of lead in bone apparently increases, and its half-life in bone is estimated to be 20 to 30 years. A daily intake of 2.5 mg lead requires nearly 4 years for the accumulation of a toxic burden, whereas a daily intake of 3.5 mg requires a few months because deposition in bone is too slow to protect the soft tissues during rapid accumulation.

Acute Lead Poisoning Acute lead poisoning is relatively infrequent(acid-soluble lead compounds or inhalation of lead vapors). Marked astringency, thirst, and a metallic taste. Nausea, abdominal pain, and vomiting . Stools may be black from lead sulfide, and there may be diarrhea or constipation. If large amounts are absorbed rapidly, a shock syndrome may develop as the result of massive GI loss of fluid. Acute CNS symptoms include paresthesias, pain, and muscle weakness. An acute hemolytic crisis sometimes causes severe anemia and hemoglobinuria. The kidneys are damaged, and oliguria and urinary changes are evident. Death may occur in 1 or 2 days.

Chronic Lead Poisoning The medical term for lead poisoning is plumbism. GIT: Anorexia, muscle discomfort, malaise, headache and Constipation. Severe abdominal pain (lead colic), is the most distressing feature of the advanced abdominal syndrome. In cases where colic is not severe, removal of the patient from the environment of exposure may be sufficient for relief of symptoms. Calcium gluconate administered IV is recommended for relief of pain and usually is more effective than morphine

Chronic Lead Poisoning

Lead palsy occurs with repeated lead exposure: Muscle weakness and easy fatigue. lead encephalopathy, is the most serious manifestation of lead poisoning and is much more common in children than in adults. The early signs of the syndrome include clumsiness, vertigo, ataxia, falling, headache, insomnia, restlessness, and irritability. As the encephalopathy develops, the patient may first become excited and confused; delirium with repetitive tonic-clonic convulsions or lethargy and coma follow. Visual disturbances also are present.

Chronic lead toxicity CDC considers a blood lead concentration of 10 mg/dl or greater to indicate excessive absorption of lead in children and to constitute grounds for environmental assessment, cleanup, and/or intervention. Chelation therapy should be considered when blood lead concentrations exceed 25 mg/dl. Hypochromic microcytic anemia, which is observed more frequently in children and is morphologically similar to that resulting from iron deficiency. Ferrochelatase is the enzyme responsible for incorporating the ferrous ion into protoporphyrin to form heme. When ferrochelatase is inhibited by lead, excess protoporphyrin takes the place of heme in the hemoglobin molecule.


Chronic Lead Poisoning Renal toxicity occurs in two forms: a reversible tubular disorder (usually seen after acute exposure of children to lead) and an irreversible interstitial nephropathy (observed more commonly in long-term industrial lead exposure). Ashen color of the face and pallor of the lips; retinal stippling; appearance of "premature aging," with stooped posture, poor muscle tone, and emaciation; and a black, grayish, or blue-black "lead line" along the gingival margin. There is a relationship between the concentration of lead in blood and blood pressure. Lead also interferes with vitamin D metabolism.

Organic Lead toxicity

Tetraethyl lead and tetramethyl lead are lipid-soluble compounds that are absorbed readily from the skin, GI tract, and lungs. The toxicity of tetraethyl lead is believed to be due to its metabolic conversion to triethyl lead and inorganic lead. The major symptoms of intoxication with tetraethyl lead are referable to the CNS: insomnia, nightmares, anorexia, nausea and vomiting, diarrhea, headache, muscular weakness, and emotional instability. Subjective CNS symptoms such as irritability, restlessness, and anxiety are next evident, usually accompanied by hypothermia, bradycardia, and hypotension.

Prevention of further exposure is important. Seizures are treated with diazepam or phenytoin , fluid and electrolyte balances must be maintained, and cerebral edema is treated with mannitol and dexamethasone or controlled hyperventilation. The concentration of lead in blood should be determined prior to initiation of chelation therapy. Chelation therapy is indicated in symptomatic patients or in patients with a blood lead concentration in excess of 50 to 60 mg/dl. A chelate is a complex formed between a metal and a compound that contains two or more potential ligands. The stability of chelates varies with the metal and the 15 ligand atoms.

Treatment of Lead Poisoning

Treatment of Lead Poisoning

Four chelators are employed: edetate calcium disodium (CaNa2EDTA), dimercaprol [British antilewisite (BAL)], Dpenicillamine, and succimer [2,3-dimercaptosuccinic acid (DMSA). CaNa2EDTA and dimercaprol usually are used in combination for lead encephalopathy. CaNa2EDTA is initiated at a dose of 30 to 50 mg/kg per day in two divided doses either by deep IM injection or slow IV infusion for up to 5 consecutive days. Dimercaprol is given IM at a dose of 4 mg/kg every 4 hours for 48 hours, then every 6 hours for 48 hours, and finally, every 6 to 12 hours for an additional 7 days.


Treatment of Lead Poisoning

Penicillamine is effective orally and may be included in the regimen at a dosage of 250 mg given four times daily for 5 days. During chronic therapy with penicillamine, the dose should not exceed 40 mg/kg per day. Succimer is the first orally active lead chelator available for children, with a safety and efficacy profile that surpasses that of D-penicillamine. Succimer usually is given every 8 hours (10 mg/kg) for 5 days and then every 12 hours for an additional 2 weeks. In any chelation regimen, the blood lead concentration should be reassessed 2 weeks after the regimen has been completed; an additional course of therapy may be indicated if blood lead concentrations rebound.

The stability of chelates varies with the metal and the ligand atoms. For example, lead and mercury have greater affinities for sulfur and nitrogen than for oxygen ligands; calcium, however, has a greater affinity for oxygen than for sulfur and nitrogen. These differences in affinity serve as the basis of selectivity of action of a chelating agent in the body. An ideal chelating agent would have the following properties: high solubility in water, resistance to biotransformation, ability to reach sites of metal storage, capacity to form nontoxic complexes with toxic metals, ability to retain chelating activity at the pH of body fluids, and ready excretion of the chelate .

Chelators A low affinity for Ca2+ also is desirable because Ca2+ in plasma is readily available for chelation, and a drug might produce hypocalcemia despite high affinity for heavy metals. The most important property of a therapeutic chelating agent is greater affinity for the metal than that of the endogenous ligands. The large number of ligands in the body is a formidable barrier to the effectiveness of a chelating agent.


Mercury was an important constituent of drugs for centuries as an ingredient in many diuretics, antibacterials, antiseptics, skin ointments, and laxatives. More specific, effective, and safer modes of therapy now have replaced the mercurials, and drug-induced mercury poisoning has become rare. However, mercury has a number of important industrial uses, and poisoning from occupational exposure and environmental pollution continues to be an area of concern. Chloralkali (e.g., bleach),Electrical equipment, Paints, Thermometers, Dental amalgams and Laboratory chemicals.


Mercury Three major chemical forms of the metal must be distinguished: mercury vapor (elemental mercury), salts of mercury, and organic mercurials. Mercury readily forms covalent bonds with sulfur, and it is this property that accounts for most of the biological properties of the metal. Even in low concentrations, mercurials are capable of inactivating sulfhydryl groups of enzymes and thus interfering with cellular metabolism and function. The affinity of mercury for thiols provides the basis for treatment of mercury poisoning with such agents as dimercaprol and penicillamine. Mercury also combines with phosphoryl, carboxyl, amide, and amine groups.

Mercury Elemental mercury is not particularly toxic when ingested because of very low absorption from the GI tract. However, inhaled mercury vapor is completely absorbed by the lung and then is oxidized to the divalent mercuric cation by catalase in the erythrocytes. CNS toxicity is more prominent after exposure to mercury vapor than to divalent forms of the metal. The soluble inorganic mercuric salts (Hg2+) gain access to the circulation when taken orally. GI absorption is approximately 10% to 15%. Insoluble inorganic mercurous compounds, such as calomel (Hg2Cl2), may undergo some oxidation to soluble compounds that are more readily absorbed. Inorganic mercury has a markedly nonuniform distribution after absorption.

Mercury The highest concentration of Hg2+ is found in the kidneys, where the metal is retained longer than in other tissues. Inorganic mercurials do not readily pass across the BBB or the placenta. The metal is excreted in the urine and feces with a half-life of about 60 days. More than 90% of Organic mercurials/methylmercury is absorbed from the human GI tract. The organic mercurials cross the BBB and the placenta and thus produce more neurological and teratogenic effects than do the inorganic salts. Methylmercury in humans is excreted mainly in the feces in the form of a glutathione conjugate. The halflife of methylmercury in the blood of humans is between 40 and 105 days 23

Mercury vapor toxicity

Short-term exposure: weakness, chills, metallic taste, nausea, vomiting, diarrhea, dyspnea, cough, and a feeling of tightness in the chest. Pulmonary toxicity may progress to an interstitial pneumonitis with severe compromise of respiratory function. Recovery, although usually complete, may be complicated by residual interstitial fibrosis. Chronic exposure: asthenic (physically weak) vegetative syndrome( neurasthenic symptoms ,goiter, increased uptake of radioiodine by the thyroid, tachycardia, labile pulse, gingivitis, dermographia (a skin condition in which red, itchy lines appear when a person scratches his or her skin), and increased mercury in the urine.

Mercury vapor toxicity

With continued exposure to mercury vapor, tremor becomes noticeable, and psychological changes consist of depression, irritability, excessive shyness, insomnia, reduced self-confidence, emotional instability, forgetfulness, confusion, impatience, and vasomotor disturbances (such as excessive perspiration and uncontrolled blushing, which together are referred to as erethism = abnormal physical sensitivity). Common features of intoxication from mercury vapor are severe salivation and gingivitis. Renal dysfunction also has been reported to result from long-term industrial exposure to mercury vapor.

Inorganic mercury toxicity Precipitation of mucous membrane proteins by mercuric salts (e.g., mercuric chloride) results in an ashen-gray appearance of the mucosa of the mouth, pharynx, and intestine and also causes intense pain and vomiting. The local corrosive effect on the GI mucosa results in severe hematochezia(passing of fresh blood in a stool) with evidence of mucosal sloughing in the stool. Hypovolemic shock and death can occur in the absence of proper treatment. Systemic toxicity: a strong metallic taste is followed by stomatitis (mouth inflammation) with gingival irritation, foul breath, and loosening of the teeth.

Inorganic mercury toxicity

The most serious and frequent systemic effect of inorganic mercury is renal toxicity(oliguria or anuria). Renal injury also follows long-term exposure, where glomerular injury predominates. The symptom complex of acrodynia also commonly follows chronic exposure. Acrodynia: mercury poisoning in young children; mercury poisoning caused by powders formerly prescribed for teething, resulting in pinkness and itching of the hands and feet, excessive sweating, low blood pressure, limpness, and insomnia

Organic Mercurials toxicity

Symptoms of exposure to methylmercury are mainly neurological and consist of visual disturbance (scotoma and visual-field constriction), ataxia, paresthesias, neurasthenia (chronic fatigue), hearing loss, dysarthria (difficulty in speech articulation), mental deterioration, muscle tremor, movement disorders, and with severe exposure, paralysis and death. Effects of methylmercury on the fetus can occur even when the mother is asymptomatic; mental retardation and neuromuscular deficits have been observed.

Treatment of Mercury Poisoning

Therapeutic measures include immediate termination of exposure and close monitoring of pulmonary status. Short-term respiratory support may be necessary. Inorganic: Prompt attention to fluid and electrolyte balance and hematological status is of critical importance in moderate-to-severe oral exposures. Emesis can be induced if the patient is awake and alert, although emesis should not be induced where there is corrosive injury.


Treatment of Mercury Poisoning

Chelation therapy with dimercaprol (for high-level exposures or symptomatic patients) or penicillamine (for low-level exposures or asymptomatic patients) is used routinely to treat poisoning with either inorganic or elemental mercury. Recommended treatment includes dimercaprol 5 mg/kg intramuscularly initially, followed by 2.5 mg/kg intramuscularly every 12 to 24 hours for 10 days. Penicillamine (250 mg orally every 6 hours) may be used alone or following treatment with dimercaprol. The orally effective chelator succimer appears to be an effective chelator for mercury, although it has not been approved by the FDA for this purpose.

The dimercaprol-mercury chelate is excreted into both bile and urine, whereas the penicillamine-mercury chelate is excreted only into urine. The short-chain organic mercurials, especially methylmercury, are the most difficult forms of mercury to mobilize from the body presumably because of their poor reactivity with chelating agents. Dimercaprol is contraindicated in methylmercury poisoning because it increases brain concentrations of methylmercury in experimental animals. Methylmercury compounds undergo extensive enterohepatic recirculation in experimental animals.

Treatment of Mercury Poisoning

Treatment of Mercury Poisoning

A nonabsorbable mercury-binding substance into the intestinal tract should facilitate their removal from the body. A polythiol resin has been used for this purpose in humans and appears to be effective. The resin has certain advantages over penicillamine. It does not cause redistribution of mercury in the body with a subsequent increase in the concentration of mercury in blood, and it has fewer adverse effects than do sulfhydryl agents that are absorbed. Conventional hemodialysis is of little value in the treatment of methylmercury poisoning because methylmercury concentrates in erythrocytes, and little is contained in the plasma.

Treatment of Mercury Poisoning

However, it has been shown that L -cysteine can be infused into the arterial blood entering the dialyzer to convert methylmercury into a diffusible form. Both free cysteine and the methylmercury-cysteine complex form in the blood and then diffuse across the membrane into the dialysate. This method has been shown to be effective in humans . Studies in animals indicate that succimer may be more effective than cysteine in this regard.


The foundations of many modern concepts of chemotherapy derive from Ehrlich's early work with organic arsenicals, and such drugs once were a mainstay of chemotherapy. Arsenic is found in soil, water, and air as a common environmental toxicant. The major source of occupational exposure to arsenic-containing compounds is from the manufacture of arsenical herbicides and pesticides. In the manufacture of both computer chips and semiconductors, metallic arsenic also may be used or produced as a by-product of the reaction chambers.

In general, toxicity increases in the sequence of organic arsenicals < As5+ < As3+ < arsine (AsH3). The organic arsenicals contain arsenic covalently linked to a carbon atom, where arsenic exists in the trivalent or pentavalent state. The organic arsenicals usually are excreted more rapidly than are the inorganic forms. The pentavalent arsenicals have very low affinity for thiol groups, in contrast to the trivalent compounds, and are much less toxic. Arsine (AsH3) is a gaseous hydride of trivalent arsenic; it produces toxic effects that are distinct from those of the other arsenic compounds.

Arsenate (pentavalent) uncouples mitochondrial oxidative phosphorylation. The mechanism is thought to be related to competitive substitution of arsenate for inorganic phosphate in the formation of ATP. Trivalent arsenicals, including inorganic arsenite, are regarded primarily as sulfhydryl reagents. As such, trivalent arsenicals inhibit many enzymes by reacting with biological ligands containing available -SH groups. The arsenite salts are more soluble in water and are better absorbed than the oxide. Experimental evidence has shown a high degree of GI absorption (80% to 90%) of both trivalent and pentavalent forms of arsenic.

Arsenic Arsenic is stored mainly in liver, kidney, heart, and lung. Much smaller amounts are found in muscle and neural tissue. Because of its chemical similarity to phosphorus, it is deposited in bone and teeth and is retained there for long periods. Arsenic readily crosses the placenta, and fetal damage has been reported. Arsenic is eliminated by many routes (e.g., feces, urine, sweat, milk, hair, skin, and lungs), although most is excreted in urine in humans. The half-life for the urinary excretion of arsenic is 3 to 5 days, much shorter than those of the other metals discussed.

Toxicity of arsenic Acute and subacute doses of inorganic arsenic induce mild vasodilation. Serious CV effects include hypotension, CHF, and cardiac arrhythmias. Long-term exposure results in peripheral vascular disease , more specifically gangrene of the extremities, especially of the feet, blackfoot disease. Myocardial damage and hypotension may become evident after more prolonged exposure to arsenic. Acute or subacute exposure to arsenic can produce GI disturbances that range from mild abdominal cramping and diarrhea to severe hemorrhagic gastroenteritis associated with shock. With chronic exposure to arsenic, GI effects usually are not observed.

Toxicity of arsenic Kidney: Initially, the glomeruli are affected, and proteinuria results. Varying degrees of tubular necrosis and degeneration occur later. Oliguria with proteinuria, hematuria, and casts frequently results. Diffuse or spotted hyperpigmentation over the trunk and extremities, cutaneous vasodilation and a "milk and roses" complexion and eventually, skin cancer. High-dose acute or subacute exposure to arsenic can cause encephalopathy; however, the most common arsenic-induced neurological lesion is a peripheral neuropathy with a stocking/glove distribution of dysesthesia (constant burning sensation). This is followed by muscular weakness in the extremities.

Toxicity of arsenic
Serious, irreversible blood and bone marrow disturbances(rare with organic arsenicals). Fatty infiltration, central necrosis, and cirrhosis. Skin, bladder ,lung, kidney, and liver cancer. Chronic exposure to arsenic has been associated with increased prevalence of diabetes mellitus, goiter, hepatomegaly, and respiratory system dysfunctions


Routine measures are taken to stabilize the patient and prevent further absorption of the poison. Hypotension requires fluid replacement and may necessitate pharmacological support with pressor agents such as dopamine. Chelation therapy often is begun with dimercaprol (3 to 4 mg/kg IM every 4 to 12 hours) until abdominal symptoms subside and charcoal (if given initially) is passed in the feces. Oral treatment with penicillamine then may be substituted for dimercaprol and continued for 4 days. Succimer is efficacious in the treatment of arsenic poisoning.

Treatment of Arsenic Poisoning

Treatment of Arsenic Poisoning

After long-term exposure to arsenic, treatment with dimercaprol and penicillamine also may be used, but oral penicillamine alone usually is sufficient. Dialysis may become necessary with severe arsenicinduced nephropathy.


Iron is an essential component of myoglobin; heme enzymes such as the cytochromes, catalase, and peroxidase; and the metalloflavoprotein enzymes, including xanthine oxidase and the mitochondrial enzyme a-glycerophosphate oxidase. Iron exists in the environment largely as ferric oxide or hydroxide or as polymers. In this state, its biological availability is limited unless solubilized by acid or chelating agents. The body store of iron is divided between essential ironcontaining compounds and excess iron, which is held in storage. Ferritin is a protein-iron storage complex that exists as individual molecules or as aggregates.


Internal exchange of iron is accomplished by the plasma protein transferrin. Adult men require only 13 mg/kg per day (about 1 mg), whereas menstruating women require about 21 mg/kg per day (about 1.4 mg). In the last two trimesters of pregnancy, requirements increase to about 80 mg/kg per day (5 to 6 mg), and infants have similar requirements due to their rapid growth. Large amounts of ferrous salts are toxic, but fatalities are rare in adults. Most deaths occur in children, particularly between the ages of 12 and 24 months. As little as 1 to 2 g of iron may cause death, but 2 to 10 g usually is ingested in fatal cases.

Signs and symptoms of severe poisoning may occur within 30 minutes after ingestion or may be delayed for several hours. They include abdominal pain, diarrhea, or vomiting of brown or bloody stomach contents containing pills. Of particular concern are pallor or cyanosis, lassitude (tiredness and apathy), drowsiness, hyperventilation due to acidosis, and cardiovascular collapse. The corrosive injury to the stomach may result in pyloric stenosis or gastric scarring. Hemorrhagic gastroenteritis and hepatic damage are prominent findings at autopsy.

Emesis Deferoxamine is poorly absorbed after oral administration, and parenteral administration is required in most cases. The drug is administered at 10 to 15 mg/kg per hour by constant infusion. For chronic iron intoxication , an intramuscular dose of 0.5 to 1.0 g/day is recommended. An orally effective iron chelator now under clinical investigation is deferiprone (1,2-dimethyl-3hydroxypyridin-4-one), Shock, dehydration, and acid-base abnormalities should be treated in the conventional manner.

Edetate Calcium Disodium The pharmacological effects of CaNa2EDTA result from formation of chelates with divalent and trivalent metals in the body. Accessible metal ions (both exogenous and endogenous) with a higher affinity for CaNa2EDTA than Ca2+ will be chelated, mobilized, and usually excreted. Because EDTA is charged at physiological pH, it does not significantly penetrate cells; its volume of distribution approximates extracellular fluid space. The main therapeutic use of CaNa2EDTA is in the treatment of metal intoxications, especially lead intoxication.

Edetate Calcium Disodium

IM administration of CaNa2EDTA results in good absorption, but pain occurs at the injection site; consequently, the chelator injection often is mixed with a local anesthetic or administered IV. For IV, CaNa2EDTA is diluted in either 5% dextrose or 0.9% saline and is administered slowly by IV drip. Rapid IV administration causes hypocalcemic tetany. Adequate renal function is necessary. The principal toxic effect of CaNa2EDTA is on the kidney. A more likely mechanism of toxicity may be interaction between the chelator and endogenous metals in proximal tubular cells.

Dimercaprol Developed during World War II as an antidote to lewisite(C2H2AsCl3), after Winford Lee Lewis (1878-1943), a vesicant arsenical war gas, hence its alternative name, British antilewisite (BAL). It is an oily fluid with a pungent, disagreeable odor typical of mercaptans. Peanut oil is the solvent employed in pharmaceutical preparations. The pharmacological actions of dimercaprol result from formation of chelation complexes between its sulfhydryl groups and metals. The concentration in plasma must be maintained by repeated fractional dosage until the offending metal can be excreted.

Dimercaprol Dimercaprol antagonizes the biological actions of metals that form mercaptides with essential cellular sulfhydryl groups, mainly arsenic, gold, and mercury. Also is used in combination with CaNa2EDTA to treat lead poisoning, especially when evidence of lead encephalopathy exists. Given by deep IM as a 100 mg/ml solution in peanut oil. The dimercaprol-metal complex breaks down easily in an acidic medium. One of the most consistent responses to dimercaprol is a rise in systolic and diastolic arterial pressures, accompanied by tachycardia. contraindicated in patients with hepatic insufficiency.

Succimer (2,3-dimercaptosuccinic acid) An orally effective chelator that is chemically similar to dimercaprol. Biotransformed to a mixed disulfide with cysteine after absorption. Produces a lead diuresis with a subsequent lowering of blood lead levels and attenuation of the untoward biochemical effects of lead. The succimer-lead chelate also is eliminated in bile; the fraction eliminated undergoes enterohepatic circulation. Does not significantly mobilize essential metals such as zinc, copper, or Fe. Adverse effects: N,V, diarrhea, and loss of appetite, Rash. Approved in the US for treatment of children with blood lead levels in excess of 45 mg/dl. 51

Penicillamine :D-,-dimethylcysteine First isolated in 1953 from the urine of patients with liver disease who were receiving penicillin. D-penicillamine is an effective chelator of copper, mercury, zinc, and lead and promotes the excretion of these metals in the urine. Well absorbed (40% to 70%) from the GIT and therefore has a decided advantage over many other chelating agents. Food, antacids, and iron reduce its absorption. Available for oral administration. For chelation therapy, the usual adult dose is 1-1.5 g/day in four divided doses. Also used in Wilson's disease and cystinuria. Adverse effects: cutaneous lesions, including urticaria, macular or papular reactions, pemphigoid lesions, lupus erythematosus, dermatomyositis etc.

Deferoxamine:deferoxamine mesylate
Isolated as iron chelate from Streptomyces pilosus and is treated chemically to obtain the metal-free ligand. Has desirable properties of a remarkably high affinity for ferric iron coupled with a very low affinity for Ca. Poorly absorbed after oral administration, and parenteral administration is required in most cases. For severe iron toxicity (serum iron levels greater than 500 mg/dl), the IV is preferred. The drug is administered at 10 to 15 mg/kg per hour by constant infusion. Rapid boluses usually are associated with hypotension. For chronic iron intoxication (e.g., thalassemia), an intramuscular dose of 0.5 to 1.0 g/day is recommended.

Deferoxamine Causes a number of allergic reactions, including pruritus, wheals, rash, and anaphylaxis. Other adverse effects include dysuria, abdominal discomfort, diarrhea, fever, leg cramps, and tachycardia. May cause neurotoxicity during long-term, high-dose therapy for transfusion-dependent thalassemia major; both visual and auditory changes have been described. A "pulmonary syndrome" has been associated with high-dose (10 to 25 mg/kg per hour) deferoxamine therapy; tachypnea, hypoxemia, fever, and eosinophilia are prominent symptoms. Contraindications: renal insufficiency and anuria; during pregnancy, the drug should be used only if clearly indicated.

Other specific Antidotes


Naxone: Opioids Flumazenil:Benzodiazepine Methylene blue: methemoglobin forming toxins Oxygen: CO Nitrites, thiosulfate or hydroxycobalamin: cyanide Vitamin K: warfarin Protamine sulfate: Heparin Vitamin B6 :INH Atropine and pralidoxime: Organophosphates Digoxin Fab fragments (Digibind):digitalis Snake venom: antivenin