Heavy Metal Toxicity

covers the major metal toxicities and pharmacological basis of the metal toxicities and antagonists

1. S VITHYA M.PHARM I YEAR

2. INTRODUCTION 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 ( e.g. antimicrobials ) have been additional sources of hazardous exposure . The burning of fossil fuels containing heavy metals, the addition of tetraethyl lead to gasoline , and the increase in industrial applications of metals have made environmental pollution the major source of heavy-metal poisoning

3. LEAD POISONING/ PLUMBISM Lead's symbol Pb is an abbreviation of its Latin name plumbum for soft metals HISTORY OF POISONING

4. SOURCE The primary sources of environmental exposure to lead are leaded paint and drinking water

5. PHARMACOKINETICS Excreted in urine and faeces excreted in bile Half life In blood-1-2 months In bone-10-30yrs

6. SYMPTOMS ACUTE

7. GIT GRAYISH LINE in the gingival margin Intestinal spasm- Lead Colic Muscle weakness and fatigue- paralysis Lead plasy Increased intracranial pressure.Lack of sensory pathway- impaired learning Lead encephalopathy NEUROMUSCULAR JUNCTION CNS Tubular disorder Interstitial nephropathy KIDNEY Antispasmodics and calcium gluconate Mannitol or by lumbar puncture CHRONIC POISONING

8. Basophil stippling Hypochromic microcytic anemia BLOOD DUE TO INHIBITION OF HEME SYNTHESIS

9. LEVELS AND SYMPTOMS

10. ORGANIC LEAD POISONING

11. DIAGNOSIS

12. CONTD…

13. TREATMENT

14. MERCURY POISONING Mercury vapor (elemental mercury), Gold minning - heat the amalgam to evaporate mercury Salts of mercury, Mercurous chloride- antiseptic, diuretic and catharatic Mercuric chloride-industries Organic mercurials - fungicide Hg is the modern chemical symbol for mercury. It comes from hydrargyrum , a Latinized form of the Greek word meaning " water-silver " since it is liquid like water and shiny like silver. The element was named after the Roman god Mercury , known for his speed and mobility

15. SOURCE

16. … PHARMACOKINETICS binds with the sulfhydryl group of enzymes to form mercaptides . inactivating sulfhydryl groups of enzymes and thus interfering with cellular metabolism and function Oral- low absorption Inhaled- converted to divalent mercury by catalase in RBC

17. PHARMACOKINETICS OF ORGANIC MERCURIALS

18. Minamata disease also was due to methylmercury . In the Japanese town of Minamata , the major industry was a chemical plant that emptied its effluent directly into Minamata Bay. The chemical plant used inorganic mercury as a catalyst, and some of it was methylated before it entered the bay. In addition, microorganisms can convert inorganic mercury to methylmercury ; the compound then is taken up rapidly by plankton algae and is concentrated in fish via the food chain. Residents of Minamata who consumed fish as a large portion of their diet were the first to be poisoned. Eventually, 121 persons were poisoned, and 46 died MINAMATA DISEASE

19. SYMPTOMS

20. ELEMENTAL MERCURY POISONING ACUTE - 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 CHRONIC - asthenic vegetative syndrome- G oiter , increased uptake of radioiodine by the thyroid, tachycardia, labile pulse, gingivitis, dermographia , and increased mercury in the urine SYMPTOMS

21. INORGANIC MERCURY POISONING ACUTE Precipitation of mucous membrane proteins by mercuric salts results in an ashen- gray appearance of the mucosa of the mouth, pharynx, and intestine and also causes intense pain, which may be accompanied by vomiting . L ocal corrosive effect of ionic inorganic mercury on the GI mucosa results in severe hematochezia with evidence of mucosal sloughing in the stool . CHRONIC stomatitis with gingival irritation, foul breath, and loosening of the teeth. The most serious and frequent systemic effect of inorganic mercury is renal toxicity. Acute tubular necrosis occurs after short-term exposure, leading to oliguria or anuria SYMPTOMS

22. PINK DISEASE: Acrodynia is an erythema of the extremities, chest, and face with photophobia, diaphoresis, anorexia, tachycardia, and either constipation or diarrhea . ORGANIC MERCURY POISONING neurological and consist of visual disturbance, ataxia, paraesthesia, neurasthenia, hearing loss, dysarthria, mental deterioration, muscle tremor, movement disorders, and with severe exposure, paralysis and death SYMPTOMS

23. DIAGNOSIS

24. FOR ELEMENTAL AS WELL AS INORGANIC POISONING 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 FOR ORGANIC POISONING Methylmercury compounds undergo extensive enterohepatic recirculation in experimental animals. Therefore, introduction of 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 TREATMENT

25. CADMIUM POISONING Cadmium meaning "calamine", a cadmium-bearing mixture of minerals, which was named after the Greek mythological character , Cadmus, the founder of Thebes) was discovered simultaneously in 1817 by Friedrich Stromeyer and Karl Samuel Leberecht Hermann, both in Germany, as an impurity in zinc carbonate.The metal was named after the Latin word for calamine, because it was found in this zinc compound Workers in smelters and other metal-processing plants may be exposed to high concentrations of cadmium in the air; Cereal grains Cigarette smoke Shell fish and animal liver and kidney

26. SOURCE

27. Half life- 10-30yrs PHARMACOKINETICS

28. SYMPTOMS Oral Intake nausea , vomiting, salivation, diarrhoea and abdominal cramps; the vomitus and diarrhoea often are bloody . Inhaled cadmium is more toxic irritation of the respiratory tract with severe, early pneumonitis, chest pains, nausea, dizziness, and diarrhea . Toxicity may progress to fatal pulmonary edema or residual emphysema with peribronchial and perivascular fibrosis

29. CHRONIC SYMPTOMS Renal toxicity Dyspnea Testicular necrosis Carcinogen TREATMENT CHELATORS- Calcium disodium EDTA DIMERCAPROL-5 days course

30. HEAVY METAL ANTAGONIST

31. Ethylene diamine tetraacetic acid (EDTA), its sodium salt ( edetate disodium, Na2EDTA), (EDTA ) PENTETIC Acid ( DTPA ) SUCCIMER DIMERCAPROL PENECILLAMINE TRIENTINE DESFERROXAMINE Administered with local anesthetic or iv slowly For radioactive poisoning Urine should be alkalized during dimercaprol therapy as their complex dissociates in acidic medium Recommended to children with lead poisoning Neurological lesion of wilson disease Neurological lesion of wilson disease For iron toxicity

32. REFERENCE BASICS AND CLINICAL PHARMACOLOGY BY KATZUNG 12 TH EDITION PHARMACOLOGY AND PHARMACOTHERAPEUTICS BY SATOSKAR 22 ND EDITION GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006)