Toxicities and manag. of poisonings (heavy metals)
Toxicities and management ofpoisonings due to Heavy Metals(Pb, Hg, As, Fe)Dr. S. Parasuraman, M.Pharm., Ph.D.,Senior Lecturer, Faculty of PharmacyAIMST UniversityLead MercuryIronArsenic
Heavy Metals poisoning• Heavy metals are commonly defined as those elements with a high(>5.0) relative density.• Heavy metals are potential to cause environmental or humantoxicity.• Heavy metal poisoning can be acute or chronic and may be causedby the following:– Lead, Mercury, Iron, Arsenic– Cadmium, Thallium, Bismuth• The metals may enter the body by:– Ingestion– Inhalation– Absorption through the skin or mucous membranes
Heavy Metals poisoning• The most common cause of heavy metal poisoning is lead.Lead poisoning is most common in affluent countries, due toremoval of lead from paint, petrol and food cans.• Mercury can be found in the elemental state (dentalamalgam, thermometers), inorganic (industrial processes) andorganic compounds (pesticides, wood preservatives, somemedicines, and contaminated fish). Ingestion of disc batteriesby children can also lead to heavy metal poisoning amongstother problems.• Poisoning from other heavy metals most often occurs inindividuals regularly exposed to the metals in their workenvironment.
Lead poisoning• Age-dependent differences in the absorption• Adult absorb 10% of an ingested dose. Children- 40%• Initially distributed to the soft tissues and slowly redistributed tobone, teeth and hair• Detected by x-ray• Half-life: 1-2 months in blood; 20-30 yr bone.– CNS: headache, confusion, clumsiness, insomnia, fatigue, impairedconcentration. Disease progresses, colonic convulsions and coma canoccur. Treated with chelation therapy. Blood lead levels 5-20 μg/dL inchildren have lower IQ levels.– GIT: Discomfort, constipation. Higher exposures can produce painfulintestinal spasms.– Blood: Hypochromic and microcytic anemia results shortenederythrocyte. Inhibit the heme synthesis enzymes.
Mercury poisoning• Toxic exposures to elemental mercury (inhaled) causes tremors,depression, memory loss, decreased verbal skills and inflammation of thekidneys. High concentrations of elemental mercury cause nonselectivepulmonary toxicity.• Exposures to inorganic salts of mercury (mercuric chloride) lead to renaldamage. Hazardous exposures of the public to inorganic forms of mercuryare uncommon.• Consumption of food substances contaminated with methylmercury (fish)cause organic mercury toxicity. Symptoms of high levels of organicmercury toxic can appear several days to several weeks after ingestion.Symptoms include visual disturbances, paresthesias, ataxia, hearing loss,mental deterioration, muscle tremors, movement disorders. With severexposure cause paralysis and death.
Arsenic poisoning• Symptoms of arsenic poisoning begin with headaches, confusion, severediarrhea, and drowsiness.• As the poisoning develops, convulsions and changes in fingernailpigmentation called leukonychia may occur.• Chronic exposure: vitamin A deficiency ---> heart disease, night blindness37 million people in more than70 countries are probablyaffected by arsenic poisoningfrom drinking water
Iron poisoning• Iron is a vital mineral in the human body.• Iron toxicity cases hemosiderosis and hemochromatosis.• Iron toxic serum level: Mild toxicity: 450-500μg/dl; sever toxicity: 800-1000 μg/dl.• Toxic effect due to hemorrhagic necrosis in GIT
Treatment for heavy metal poisoning• Chelation Therapy– Chelation agent + Metal = Chelate– A chelating agent is chemical compound or drug moleculecapable of forming a heterocyclic ring with a metal ion asits closing member.
Dimercaprol• Dimercaprol/ British Anti Lewisite/ BAL (Oily nature)• SH group of dimercaprol bind with heavy metal and form sulfhydrylcomplex• Two molecule of dimercaprol with one metal ion is more stable than 1:1complex.• Dimercaprol produce dose dependent toxicity (large amount should notbe given)• It’s a narrow therapeutic agent and produce serious side effects includesnephrotoxicity and hypertension.• Used for Heavy metal (As, Hg, Au, Bi, Ni and Sb) poisoning and Wilsonsdisease (autosomal recessive genetic disorder in which copperaccumulates in tissues).• Dimercaprol metabolized in liver by glucuronide conjugation and excretedin 4-6 h.• Dimercaprol-metal complex dissociated faster in acidic urine and therelease metal can damage kidney.
Dimercaprol• Adverse effects:– Rise in BP, tachycardia, vomiting, tingling and burning sensations,inflammation of mucous membranes, sweating, cramps, headache andanxiety.– Antihistaminics given 30 min before dimercaprol injection to reduceintensity of adverse effects.Dimercaptosuccinic acid• Similar to dimercaprol in chelating properties, water soluble,less toxic and orally effective.• Side effects: Nausea, anorexia and loose motions.Cont.,
Calcium disodium edetate• Calcium chelate of Na2 EDT A.• higher affinity with Pb, Zn, Cd, Mn and Cu and someradioactive material.• Not ionized in G.I.T. administered i.v route.• Brain and CSF: Not cross BBB.• Use:– Lead poisoning- 1 gm is diluted to 200- 300 ml in saline or glucosesolution and infused i.v. over 1 hour twice daily for 3-5 days.• Adverse effects:– Relatively safe.– Kidney damage with proximal tubular necrosis is the most importantproblem.– Anaphylactoid reaction with fall in BP.
Penicillamine• Product of penicillin.• d-isomer is active heavy metals. l-isomer produce opticneuritis and are more toxic.• Use:Used for the treatment of– Wilsons disease (genetic disorder, copper accumulates in tissues).– Chronic lead poisoning.– Copper/mercury poisoning.– Cystinuria and cystine stones.• Adverse effects– Short-term administration: Safe.– Long-term use: Dermatological, renal, haematological and collagentissue toxicities.
Desferrioxamine• High affinity with iron• One gram capable of chelating 85 mg of elemental iron• Stable nontoxic complex - excreted in urine.• Route of administration:– Oral absorption: poor– Parenteral: preferable• Use:– Acute iron poisoning (for children)– Transfusion siderosis• Adverse effects– Cause histamine release– abdominal pain, loose motions, muscle cramps, fever and dysuria
Deferiprone• Orally active iron chelator• Treatment of transfusion siderosis in thalassemia patients.• Iron chelator used to clear iron overload.• Side effects– Anorexia, vomiting, altered taste, joint pain, reversible neutropenia,rarely agranulocytosis