Download as PDF, PPTX
Heavy Metals And Chelating Agents ppt.pptx.pdf
- 1. Heavy Metal Poisoning AndChelating Agents Dr Veena V Dept of Pharmacology BMCRC, Ballari
- 2. INTRODUC TION Toxicology deals withtoxic effects of drugs & various chemicals in use Chemicals : Air pollutants, Environmental pollutants, Agricultural pollutants, Industrial solvents & Heavy metals Heavy metals: Pb, Cu, Hg, Fe, As etc Poisoning can be suicidal, homicidal, accidental or occupational Specific antidotes are for heavy metals, OP compounds, Methyl alc & Cyanides
- 3. General measures inTreatment of Poisoning 1) Provide support for Vital functions (ABC) 2) Symptomatic 3) Specific antidote 4) Decontaminate skin, eyes & GIT • Thorough washing of affected parts with soap/ shampoo & lukewarm water • Flush eyes with saline or water along with LA drops • GIT: a) Emesis –Ipecac syrup (30ml in 250ml of water within 30 min of ingestion) Avoid it in corrosives, petroleum products, strychnine poisoning & in unconscious and convulsing pts
- 4. b) Gastric lavage c)Cathartics : 10% MgSO4 or 70% Sorbitol d) Whole bowel irrigation: PEG( Polyethylene Glycol) e) Activated Charcoal: Adsorbs almost all poisons & drugs Avoid in (I LAC): Iron, Lithium, Alc, Corrosives or Cyanide poisoning Unconscious/Convulsing pts Intestinal obstruction Pts who need endoscopic examn Avoid Emesis/ Cathartics along with this ( Charcoal removes Emetics/ Cathartics, Causes Dehydration) 0.5-2g/kg in water, given oral/ via gastric tube Repeat 20-30g every 4hrs
- 5. 5) Hemoperfusion 6) Hemodialysis 7)Peritoneal dialysis 8) Urinary manipulation: Alkalanise urine in acidic drug poisoning using Sod bicarb Acidify urine in basic drug poisoning using Ascorbic acid Avoid acidification of urine in presence of myoglobinuria/ Rhabdomyolysis 9) Treatment of heavy metals by Chelating agents
- 6. Heavy Metal Poisoning • Poisoningwith lead, mercury, iron, copper, arsenic & nickel occur in persons working in mines, industries of glass, paint, pesticides & petroleum. • Heavy metals combine with the functional groups( ligands) of vital enzymes, interfere with enzymes functioning & exert their toxic effects • Metals are treated by chelating agents
- 7. ARSENI C • Exists astrivalent & pentavalent salts & gas form which is most toxic. • It is an environmental & occupational hazard • Is a carcinogen, causes Ca of lungs & skin Acute Poisoning: Dose: 100-200mg S/S • Sweet garlicky odour to breath & stool • Nausea, vomiting, GE- bloody or rice water stools with mucous & abd cramp • Painful cramps in legs • Laryngitis • Dehydration & shock • Dilated pupils • Cardiotoxic: Prolonged QT interval, arrhythmias • Inhalational: Hemoptysis, pulm oedema, patchy infiltrates, intravascular hemolysis- Hburia, jaundice, Ac renal failure (Arsine gas)
- 8. • ARDS • Hepatitis •Skin : Mee’s lines, Alopecia, Macular rash, Pigmentation • Ac encephalopathy, Convulsions, Coma • Glove & stocking type Peripheral neuropathy • Peripheral sensorimotor neuropathy mimics GB syndrome Mechanism of toxicity of Arsenic Arsenic inhibits pyruvate dehydrogenase ↓ Citric Acid Cycle activity ↓ Gluconeogenesis • Also arsenic ↑ Free radicals production
- 9. Chronic Arsenic Poisoning StageI: Nutritional & GIT disturbances Stage II: Catarrhal Changes Stage III: Skin changes Stage IV: Nervous disturbances Also Bone Marrow Depression
- 11.
- 13. LEAD • Lead poisoningoccurs through cooking or storing food in utensils containing lead • Children eating lead based paints • Occupational exposure in mine workers, smelters and lead battery workers Acute Poisoning S/S: • Anemia Pb inhibits heme synthesis • Porphyrinuria & ↑ Porphyrin excretion • Renal Tubular damage • Neuropathy • Encephalopathy, leg cramps arthralgia, limb paralysis • Metallic taste, Abd Pain
- 14. Chronic Pb poisoning(Plumbism) • Lethargy, weakness • Tremors, Anorexia, wt loss • GIT disturbances: Constipation, colicky pain • Burton’s line : Blue line on the gums • Wrist drop/ foot drop (Peripheral extensor muscles paralysis) • Nephritis • In children: Growth retardation, Neurocognitive deficits, ↓IQ • Microcytic hypochromic anemia • Basophilic stippling/ Punctate basophilia PK: Orally absorbed, widely distributed to bone, brain, kidneys, liver Excreted thr Kidneys, feces, bile, skin, hair, nail, sweat & breast milk Burton”s line
- 15. Treatment Ac poisoning • Gastriclavage: Sod or MgSO4 • Morphine or Atropine to relieve colic • Calcium Disodium EDTA ( Chelating agent) Chr Poisoning • Gastric lavage • 5% DNS • Morphine or Atropine 1g bd upto 5 days • BAL : 4mg/kg every 4 hrs
- 16. MERCUR Y • Inorganic &Organic salts, Organic is most imp toxicologically • Elemental Hg is not absorbed from GIT & is non toxic • Minimata disease: By eating fish containing high conc of Methylmercury (org) S/S: Inhaled as vapours • Chest pain, dyspnea • Nausea, vomiting, GE • Kidney & CNS damage Ac poisoning • Metallic taste • Vomiting • Profuse, bloody, painful purging • Foul breath • Ac tubular necrosis
- 17. Chr Poisoning • Gingivostomatitis •Loosened teeth • GE • Renal toxicity • CNS: Hallucinations, Mania, Insomnia Hatter’s Shake (Tremors) • Minimata disease: Birth defects Erethism: CNS toxicity with Behavioural changes (Irritable, memory loss, depression, Personality derangement)
- 18. Hemodialysis, if reqd Forchr poisoning: Same+ Belladona30mg tid
- 19. CHELATING AGENTS • Metal poisoningis treated using chelating agent • Greek word ‘Chele’ meaning claw • A chelating agent contains polar groups which bind to metal ions similar to that of endogenous ligands. • Thus compete with body ligands & form stable, nontoxic, water- soluble complex which is excreted easily from the body • These are agents which bind to metal & prevent or reverse the binding of metallic cations to ligands within the body
- 21. Chelating Agents: • BAL/ Dimercaprol • D- Penicillamine • Calcium Disodium Edetate / EDTA (Ethylene Diamine Tetra- acetic acid) Disodium calcium salt • Succimer • Unithiol • Trientine • Desferrioxamine/ Deferoxamine • Deferiprone • Deferasirox
- 22. Dimercaprol/ British Antilewisite • Discoveredduring world warII as antidote for Arsenical gas Lewisite • Given IM in a pea nut oil vehicle, • 2 BAL molecules combine with 1 Atom of Hg to form a non toxic complex which dissociates faster in acidic urine. So alkalinize urine when this is given • Dose: 5 mg/kg IM stat followed by 2-3mg/kg 8hrly for 2days, then od for 10 days • CI: Iron poisoning ( coz BAL-Fe complex is toxic) • USES: Poisoning with Hg, As, Pb, Cu, Au, Bi, Ni, Sb • A/E: Pain at inj site Sweating Headache Cramps Tachycardia Mild HTn Tingling & burning sensation in extremities To reduce A/E intensity Antihistamine given 1/2hr before giving this
- 23. Succimer • Structural analogueof Dimercaprol • Effective orally, less toxic • USES: Pb poisoning- 10mg/kg 8th hrly x 5days, later 10mg/kg bd x 14 days Hg, Cu, Zn poisoning • A/E: Anorexia, Nausea, Diarrhea ↑ liver transaminases & rashes- rare UNITHIOL • Structural analogue of Dimercaprol • Given oral/IV • USES: Hg- Ac Poisoning Arsenic- Ac poisoning Pb • Dose: IV infusion3-5mg/kg 4th hrly After condn is stable, oral 4-8mg/kg 6th hrly • A/E: Mild urticaria Rapid IV – Vasodilation & hTN
- 24. D- Penicillamine Water solubledegraded product of Penicillin d-isomer is used. L isomer & racemate cause optic neuritis Uses: • Drug of choice in treatment of Wilson’s disease • In Cu poisoning: Dose- 500mg bd, 2hrs after meals ( to prevent chelation of other dietary metals) • Hg, Pb poisoning • Cystinuria & Cystine stones– complexes with cystine • Scleroderma: ↑solubility of collagen • Rhematoid arthritis- rarely • A/E: Hypersensitivity Aplastic anemia Leucopenia Vit B6 deficiency Proteinuria (rare) TRIENTINE • Alternative to D-Penicillamine • Less toxic • Given oral- 1gbd on empty stomach • A/E: Iron def anemia
- 25. CALCIUM DISODIUM EDTA • Highlypolar- only extracellularly • Not absorbed from GIT • Doesn’t cross BBB • IM very painful. So given slow IV • EDTA is a strong chelator of Ca Hypocalcemia. So given as it’s Disod Ca salt • USES: Pb poisoning- 50-75mg/kg/day for 3-5days, 6th hrly slow IV + Dimercaprol 4mg/kg 4th hrly for 3-5 days Chelator of Pb, Zn, Cd, Mn, Fe, Cu • A/E: Nephrotoxic- Tubular necrosis hTN Myalgia Lacrimation Nasal congestion
- 26. DESFERRIOXA MINE • Iron chelator,obtained from Streptomyces pilosus • 1g chelates 85mg of iron • Removes iron from ferritin, hemosiderin & transferrin but not from Hb • Dose: Severe iron Toxicity: IV infusion 10-15mg/kg/hr Moderate toxicity : IM 50mg/kg Chr toxicity : IM 0.5-1.0g/day Thalassemia : IV infusion 15mg/kg/hr given to↓Fe overload, 2g for every unit of blood • Also used for Aluminium toxicity • A/E : Rapid IV infusion- Diarrhea, hTN Others: GI symptoms & dysuria High dose- Flushing, urticaria, rash & ARDS (rare) Repeated use- Changes in lens & retina
- 27. DEFERIPRONE • Orally effectiveiron chelator • Also used in hepatic cirrhosis • A/E: Anorexia, altered taste Joint pain Reversible neutropenia Prolonged use- Zn depletion DEFERASIROX • New oral iron chelator • Given od • Complex formed is excreted thr bile • A/E: GIT upset Headache Pruritus Skin discolouration Rash