Please enable JavaScript.
Coggle requires JavaScript to display documents.
CHELATING AGENTS - Coggle Diagram
CHELATING AGENTS
Dimercaprol (British antilewisite; BAL)
oily, pungent smelling, viscous liquid, developed during World War II by Britishers as an
antidote to the arsenical war gas lewisite
two SH groups of dimercaprol bind those metals which produce their toxicity by interacting with sulfhydryl containing enzymes in the body
2:1
dimercaprol- metal ion complex is more stable
USES
Poisoning by A
s, Hg, Au, Bi, Ni, Sb:
i.m., 5 mg/kg stat, followed by 2–3 mg/kg every 4–8 hours for 2 days, then OD/BD for 10 days
Dimercaprol-metal complex
dissociates faster in acidic urine
→ kidney damage → urine is alkalinized
As an
adjuvant
to Cal. disod. edetate in lead poisoning.
As an
adjuvant
to penicillamine in Cu poisoning and in Wilson’s disease—300 mg/ day i.m. for 10 days every second month
CONTRAINDICATIONS
:red_cross:
Iron & Cadmium poisoning
→ dimercaprol-Fe & dimercaprol-Cd complex → Toxic
ADVERSE EFFECTS
:warning:
Rise in BP & HR, vomiting, tingling, burning sensations, inflammation of mucous membranes, sweating, cramps, headache, anxiety
reduced by
pretreatment with antihistaminics
Drugs which complex metal ions forming ring structures within their molecule
5-7 membered ring
– most stable
Primary use -
heavy metal poisoning
Desferrioxamine
long chain iron containing complex obtained from an
actinomycete
Chemical removal of iron from it yields desferrioxamine -
very high affinity for iron
1g → 85 mg of elemental iron
straight chain desferrioxamine molecule winds round ferric iron → stable nontoxic complex → urine
removes loosely bound iron as well as that from haemosiderin and ferritin, but not from haemoglobin or cytochrome
Has low affinity for calcium.
USES
•
Acute iron poisoning
-mostly in children
-most important indication of desferrioxamine, which may be life saving
•
Transfusion siderosis
-occurs in thalassemia patients who receive repeated blood transfusion
-Desferrioxamine 0.5–1 g/day i.m.
-It may also be infused i.v. concurrently with blood transfusion - 2 g per unit of blood
A/E
•
histamine release
→ ↓BP, flushing, itching, urticaria and rashes
•
Changes in lens & retina
on repeated use
•abdominal pain, loose motions, muscle cramps, fever, dysuria
Dimercaptosuccinic acid (Succimer)
Similar to dimercaprol in chelating properties, water soluble, l
ess toxic, orally effective
Uses:
As,Hg, Pb poisoning, also chelates Cu, Zn
A/E:
nausea, anorexia, loose motions
PROPERTIES OF CHELATING AGENT
-Chelating agents compete with body ligands for the heavy metal; differ in their affinity for different metals
-Should have a higher affinity for the toxic metal than for
calcium
-Should also have higher affinity than the
body ligands
for the toxic metal
-Distribution in the body should correspond to that of the metal to be chelated
-Should be
water soluble
Disodium edetate (Na2EDTA)
Disodium salt of ethylene diamine tetraacetic acid
Potent chelator of
calcium
—causes
tetany on i.v.
slow iv infusion
→ tetany does not occur, because calcium is withdrawn from bones
Uses:
Emergency control of hypercalcaemia: 50 mg/kg i.v. Infusion over 2–4 hours (Bisphosphonates preferred)
Calcium disodium edetate (Ca Na2 EDTA)
Calcium chelate of Na2 EDTA
higher affinity for metals like
Pb, Zn, Cd, Mn, Cu
and some radioactive metals
Highly ionized → distributed only extracellularly; rapidly excreted in urine by glomerular filtration (t½ < 1 hour)
not absorbed from the g.i.t.—must be given parenterally - preferred route is
i.v.
USES
Lead poisoning
– primary indication
Fe, Zn, Cu, Mn and radioactive metal
poisoning
Not useful in Hg poisoning
→ Hg is more firmly bound to body constituents; localized in areas not accessible to CaNa2 EDTA
A/E
•
Proximal renal tubular necrosis
- minimized by maintaining high urine flow
•Acute febrile reaction •Anaphylactoid reaction
Does not cause tetany - safe
Penicillamine
Dimethyl cysteine, obtained as a degradation product of penicillin
Selectively chelates
Cu, Hg, Pb and Zn
d-isomer
used therapeutically; l-isomer and the racemate → optic neuritis
It is adequately absorbed after oral administration, little metabolized in the body; excreted in urine and faeces
USES
Wilson’s disease (Hepatolenticular degeneration)
•genetic deficiency of
ceruloplasmin
, a protein which normally binds and disposes off Cu from the body → free Cu gets deposited in liver, sub
stantia nigra, basal ganglia of brain
and causes local degeneration •
Life long therapy
is needed to prevent progression
Copper or Mercury poisoning
•
DOC for Cu
poisoning •alternative drug to Dimercaprol/ Succimer for Hg poisoning
Chronic Lead poisoning
•
adjuvant
to CaNa2EDTA, Succimer is preferred.
Cystinuria and Cystine stones
•promotes the excretion of cysteine and prevents its precipitation in the urinary tract, because
penicillamine-cysteine complex is more soluble
than dicysteine (cystine).
Scleroderma
•by increasing soluble collagen
ADVERSE EFFECTS
Short term use
Cutaneous reactions
Itching
Febrile episodes
Long term Use
Dermatological, Renal, Haematological & Collagen tissue toxicities
Deferasirox
Oral iron chelator
Uses:
chronic iron overload due to repeated blood transfusion, non-transfusion dependent thalassaemia syndromes
Low affinity for Cu, Zn
A/E:
nausea, epigastric pain, headache, pruritus, rashes, skin discolouration, rarely g.i. ulceration, haemorrhages, proteinurea, renal failure
20 mg/kg OD on empty stomach and no food for next 1 hr
Deferiprone
Oral iron chelator
Uses:
transfusion siderosis in thalassemia patients, acute iron poisoning, iron overload in hepatic cirrhosis
Less effective alternative to injected desferrioxamine
A/E:
anorexia, vomiting, altered taste, joint pain, reversible neutropenia, rarely agranulocytosis