Heavy Metal Chelation Therapy and Treatment Options
Learn about the properties of toxic metals in the periodic table and common implicated metals like Lead, Mercury, Arsenic, and Cadmium. Discover the process of chelation therapy, chelating agents, and specific chelators used, such as Dimercaprol, D-Penicillamine, and Desferrioxamine. Find out how these agents form complexes with heavy metals to facilitate their removal from the body.
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Presentation Transcript
80 metals in periodictable They have corrosive & astringentproperties Act as a protoplasmic poison by inhibiting essentialenzymes Exert toxic effects bycombining with andinactivating functional groupsof enzyme like SH, NH2, OH
Commonly implicatedmetals Lead Mercury Arsenic Cadmium
Process of an equilibrium reaction between a metal ionand a complexing agentthat produce a stable, nonionized, non toxic & water soluble complexes which canbeeliminated easily. Chelatingagents Agents having ability to form complexes with heavy metal and prevent or reverse the bindingof metallic cation to ligands ofthe body
More affinity for metalsthan endogenousligand High solubility inwater Resistance to biotransformation Form non toxic complexes with toxicmetal Acceleratemobilization and/or removal of the metals Cheap and easy to administer Easy excretion of chelatingcomplex
1. Dimercaprol(BAL),Succimer(DMSA),DMPS 2. D-Penicillamine & N-acetylpenicillamine 3. EDT Aderivatives 4. Desferrioxamine,Deferiprone,Defrasirox 5. Trientene
Synthesized by Stocken and Thompson during world warII Developed as antidote to lewisite ( arsenical wargas) BAL-British antilewisite Oily, Pungent smelling, Viscousliquid
Form poorly dissociable complex with metalions Protect the SHenzymes Prevent inhibition ofenzyme Reactivates the inhibiting enzymes( amount andduration) P/K Can t be givenorally Given bydeepIM injection Short t1/2,Peak plasma level in 1/2hrs -1 hr(IM) Metabolized in 6hrs and excreted asglucuronide
Poisoning byAs,Hg,Pb Dose 5mg/kg stat, followed by 2-3 mg/kg every 4-8hrsfor 2 days and then twice daily for10 days As an adjuvant to edetate in Leadpoisoning As an adjuvant to penicillamine in Wilson sdisease C/I Hepaticdisease Iron and cadmiumpoisoning
Injection is painful and Chances of sterileabscess Allergicreaction Nausea, vomiting, headache Lacrimation,Conjuctivitis Sialorrhoea,paresthesia,musclepain Hemolysis in G-6PDdeficiency Anginal pain, Tachycardia,Hypertension
Synthesized 1940s by British chemist L.N.Owen Water soluble analogue ofdimercaprol P/K Orallyadministered Absorption rapid butvariable Rapid and extensive hepaticmetabolism 90% cysteine disulfides, 10%unchanged
Leadpoisoning As, Cd, , Hg SideEffects GI - nausea, anorexia, vomiting,diarrhea Weakness, dizziness,rash Transient elevation of hepatic transaminaseenzymes
Dimercaptopropane sulphonate Water solubleanalogue Used orally andIV Usedin severeacute poisoning withAsand Hg A/E Skinreaction
Degradation product ofpenicillin D-isomer Morepotent P/K Well absorbedorally Absorption is inhibited by foods, Fe,antacids Peak plasma conc. In 1-3hr Metabolized inliver
1.For Cu, Hg, Pbpoisoning 2.Wilson s disease( Hepato lenticulardegeneration) Dose 1-2gm/day in four dividedodses 3.Otheruses Rheumatoid arthritis(DMARD) Cystinuria Primary biliary cirrhosis andscleroderma
Generaltoxicities Headache, rash, fever,lymphadenopathy, dysguesia(taste) Hematologicaltoxicities Aplastic anemia, agranulocytosis,thrombocytopenia Autoimmunesyndrome Good pasture's Syndrome, MyastheniaGravis Others Drug fever, polyarthritis, exfoliativedermatitis
Cupriureticagent Useful in wilson sdisease Less potent but safer than d-penicillamine A/E Anemia Dose 2gm in adult in 2-4 divideddoses
Obtained from streptomycespilocus Chelator ofiron Removesiron from hemosiderin andferritin but not from hemoglobin andcytochrome M.O.A Bindferric iron to form ferrioxamine (stable ,water soluble) P/K Poorly absorbed after oral administration ,Usedparenterally Metabolized by enzyme present inplasma
Acute Irontoxicity 10-15mg/kg/hr constantinfusion 50mg/kg IM For chronic ironintoxication ( 0.5 to 1gm/day,IM) For chelation of aluminum in dialysispatient
Allergic reactions(pruritus, wheal,rash) Dysuria, abdominal discomfort,diarrhea Cataract,neurotoxicity Pulmonarysyndrome C.I Renaldisease Pregnantwomen
Orally effective but less effective thendesferrioxamine Use In patient in whom desferioxamine is C .I ,unacceptable or not tolerated. A/E Anorexia,Vomiting,Joint pain, Blooddyscrasia Dose50-100mg/kg daily in 2-4 divideddoses
Orallyeffective Use Use when desferrioxamine is C I Iron overload A/E GIulceration Fanconi like syndrome Dose20-30mg/kg
EDTA,Calcium EDTA,Edetate calciumdisodium Chelates divalent or trivalentmetals Chelates extracellular metal ions more thanintracellular ions P/K Not absorbedorally Doesn t crossBBB IM injection-Painful
Leadpoisoning Acutepoisoning Slow iv , 40mg /kgin two divided doses /day for5days Fe,Zn,Cu,Mn, Cd,poisoning Not useful for Hg poisoning
Thromboplebitis Nausea,diarrhea Oliguric renalfailure Febrile reaction, myalgia, rhinorhea Lacrimation,dermatitis Hypocalcaemic tetany(rapid IVinfusion)
Used in cyanidepoisoning Diagnosis must becorrect Cobalttoxicity
Chelatingagent Ca NaEDT A Desferioxamine Deferiprone DicobaltEDT A Dimercarpol(BAL) Succimer D-Penicillamine Use inpoisoning Lead Iron,Aluminium Iron Cyanide Arsenic,Mercury,Lead,Cu,Au Cu,Hg,Pb Cu
