• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Chelating agent - drdhriti
 

Chelating agent - drdhriti

on

  • 1,270 views

A Power point presentation on "Chelating agents" suitable for UG MBBS level Medical students

A Power point presentation on "Chelating agents" suitable for UG MBBS level Medical students

Statistics

Views

Total Views
1,270
Views on SlideShare
1,270
Embed Views
0

Actions

Likes
2
Downloads
79
Comments
1

0 Embeds 0

No embeds

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel

11 of 1 previous next

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment
  • Disodium edetate <br />

Chelating agent - drdhriti Chelating agent - drdhriti Presentation Transcript

  • Chelating Agents Dr. D. K. Brahma Department of Pharmacology NEIGRIHMS, Shillong
  • What are they ??? • These are the compounds mainly used in heavy metal poisoning ▫ Combines (complex) with metallic ions, forming ring structures within their molecule (Chele – crab) ▫ Form stable, non toxic and easily exretable complexes with toxic metals ▫ Contains 2 or more reactive groups (ligand) such that can hold metal from two sides ▫ Ligand: is a functional group capable of forming coordinate bond in which both the shared electrons are donated by ligand – mostly O, N or S atom in hydroxyl, carboxyl, keto, sulhydryl, disulfide, amino or phosphate groups.
  • Chelating Agents - MOA • Heavy metals exert their toxic effects by combining with and inactivating functional groups (ligands) of enzymes and important biomolecules - sulfhydril, hydroxyl, carboxyl etc. leading to inactivation • Chelating agents compete with body ligands for the heavy metal – also differ in affinity for different metals • Chelating agents have high affinity for such metals and combine with them to form non toxic and water soluble complexes for elimination • Possesses: –ve charged groups to attract +ve charged toxic metals
  • Ideal chelating agent 1. Ideal chelating agents have higher affinity for toxic metals than for body Ca++ (readily available in plasma and ECF) 2. Should also have higher affinity for toxic metals than body ligands 3. Ideally should be water soluble and distribution should correspond to that of the metal intended to Interval of administration between exposure to metals and chelating agents should be less
  • Chelating Agent - Classification 1. Dimercaprol (British antilewisite) or BAL – As, Au, Bi, Ni, Sb and Hg poisoning 2. Dimercaptosuccinic acid (succimer) - Pb 3. Calcium disodium edetate (EDTA) – lead poisoning 4. Disodium edetate 5. Penicillamine – Cu, Pb, Hg, Zn 6. Desferrioxamine – Iron overload 7. Deferiprone - Iron
  • BAL or Dimercaprol: • World War-II as anti-Lewisite • Oily , pungent smelling, viscous liquid, water insoluble Pharmacological actions: ▫ heavy metals like As, Hg, Au, Bi, Ni, Sb and Cu etc. attacks (-SH), an important component of CoA and prevents formation of acetyl CoA leading to disaster - BAL binds with these metals and protects CoA ▫ 1:1 Vs 2:1 Complex (more stability) – excess amount is required  Metal-BAL complex dissociates quickly releases metal slowly – BAL partly metabolized in the body  BAL is oxidized in the body ▫ Alkalinazation of urine is required – in acid urine complex dissociates faster ▫ However dose dependent toxicity – no large dose at time
  • BAL – contd. • Uses: 1. Poisoning by As, Hg, Au, Bi, Ni and Sb etc.  Dose: Given I/M in 10% solution in oil - Available as 2 ml ampoules (50 mg/ml)  Given deep IM 5 mg/kg stat every 4 Hrly for 2 days followed by increase in interval after 3rd day 1. As adjuvant to Cal. disod. edetate in Lead Poisoning 2. As adjuvant to Penicillamine in Cu poisoning • ADRs: Unpleasant nausea, vomiting, burning sensation of mouth, inflammation of mucous membranes, sweating, cramps and lacrimation etc. • Contraindicated in hepatic damage and Cd and Fe poisoning
  • Penicillamine • • • • • Degraded product of Penicillin (beta dimethylcysteine) Prepared by alkaline hydrolysis of benzyl penicillin – d-penicillamine Strong Cu chelating property - useful in Cu poisoning MOA is same as others – selective chelating of Cu, Hg, Pb and Zn Absorbed orally - available as 250 mg capsules, metabolized in liver and excreted in urine • Uses: ▫ Wilson`s disease: hepatolenticular degeneration due to genetic deficiency of ceruplasmin (Cu deposition in body) – life long therapy (0.5-1 gm daily) ▫ Cu and Hg (alternative) Poisoning ▫ Chronic Pb poisoning (adjuvant to edetate) ▫ Cystinuria and cystine stones ▫ Scleroderma: benefits by increasing soluble collagen • ADRs: Cutaneous dermatological reactions ▫ ▫ ▫ ▫ General: headache, sore throat, fever, rash, loss of taste, neuritis Blood: leucopenia, thrombocytopeenia, aplastic anaemia etc. Renal: nephrotic syndrome, haematuria Autoimmune: Myaesthenia like syndrome, diabetes, SLE etc.
  • Calcium disodium edetate (CaNa2EDTA) • Calcium chelate of Na2EDTA is used clinically instead of Na2EDTA – ethylene diamine tetracetic acid • High affinity for Pb, Zn, Cd, Mn, Cu and some radioactive metals • MOA: Removes the metals by exchanging with Ca++ • Highly ionized – not absorbed orally and that’s why acts extracellularly – rapidly excreted via kidney • Given IV as not absorbed in gut – IM is painful • No CSF penetration • Uses: • Lead Poisoning – 1 gm is diluted in 200-300 ml of NS infused over 1 hr twice daily – 2nd course repeated after 1 week • Fe, Zn, Cu and Mn poisoning – but not in Hg poisoning • ADRs: 1. Kidney damage – toxic metal dissociate in tubule – should enhance urine flow; 2. febrile reactions – chills, body ache, malaise, tiredness etc. 3. Anaphylactoid reactions
  • Desferrioxamine (Acute Iron Poisoning) • Ferrioxamine – an Iron containing compound – actinomycetes ▫ Chemical removal of Iron – desferrioxamine ▫ 1gm = 85 mg of elemental iron • MOA: Desferrioxamine binds with ferric Iron – stable nontoxic compound ▫ Also removes Iron (loosely bound) from haemosiderin and ferritin, but not Hb and Cyt. ▫ Low Ca++ affinity • Uses: SC or IV (0.5 gm/vial ) 1. Acute Iron Poisoning 2. Transfusion siderosis: –– 0.5-1 gm/day SC or with Blood transfusion 2 gm /unit of blood • ADRs: Histamine release – fall in BP and alleric reactions
  • Acute Iron Poisoning • Common in infants and children – 10 to 20 mg iron tablets or equivalent (above 60 mg/kg) • Symptoms: Vomiting, abdominal pain, haematemesis, diarrhoea, lethargy, cyanosis, dehydration, acidosis, shock, convulsion and death • Pathology: haemorrhage & inflammation in gut, hepatic necrosis and brain damage • Aim of treatment: To induce vomiting or gastric lavage with sodibicarb, egg yolk or milk - orally to complex Iron • Desferrioxamine: To bind the iron already present ▫ 50 mg/kg IM/SC every 4-12 Hrly till serum levels of Iron falls below 200mcg/dl ▫ Or IV 10-15 mg/kg/hr till serum Iron falls below 200 mcg/dl ▫ Supportive therapy with fluid and correction of acidosis etc.
  • Deferiprone • Orally active Iron chelator • Given in transfusion siderosis in thalassemia patients • Also used in iron poisoning but less effective than desferrioxamine • Dose: 50 to 100 mg/kg in daily in 4 divided doses • ADRs: Joint pain, anorexia, vomiting and agranulocytosis etc.
  • Important • Short Questions on – BAL, Penicillamine, Calcium edetate and Deferiprone – all are important • Acute Iron Poisoning management Desferrioxamine
  • Thank you - - All the Best