CHELATORS PT.

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 PENICILLAMINE
D-Dimethlcysteine
White, crystalline,
water-soluble derivative
of PCN
Less toxic than L isomer
The preferred
therapeutic form
Readily absorbed from
the gut
Resistant to metabolic
degradation
 Indications & Toxicity
Used 1 for tx of copper poisoning or
to prevent copper accumulation
Wilsons dse (hepatocellular
degeneration)
Tx of severe rheumatoid arthritis
OPD: inc. urinary Pb and Hg
Replaced by succimer (stronger metal-
mobilization and lower adverse fx profile
 Adverse fx
Hypersensitivity rxn
Rash, pruritus, drug fever
Ext caution: Hx of PCN allergy
Nephrotoxicity with
proteinuria
Renal insufficiency
Pancytopenia
Pyridoxine defiency (rare in
D form)
N-acetylpenicillamine
Experimental in Hg
poisoning, superior metal-
mobilizing capacity
Not commerically available
 EDETATE CALCIUM
DISODIUM
EDTA
(Ethylenediaminete
tracetic acid)
Efficient chelator of
many divalent and
trivalent metals in
vitro
Calcium disodium
salt
To prevent
potentially life-
threatening
 Penetrates cell membranes relatively poorly,
so chelates extracellular metal ions much more
effectively than intracellular ions.
Oral absorption is limited by high ionic polarity
Oral: may increase Pb absorption from the gut
Should be administered by IV
Rapid excretion by glomerular filtratx
50% in urine in 1 hr
Mobilizes Pb from soft tissues marked inc in
urinary Pb excretion, deccline in blood conc
Delayed excretion and metal-mobilization in px with
renal insufficiency.
 INDICATIONS
Chelation of Pb
Zn, Mn, heavy radionuclides
Alernative med: no usefulness in tx of
artherosclerosic cardivascular dse.
Contraindicated in anuric px
Low doses + hemodialysis/hemofiltration
Nephrotoxicity
Mostly prevented by maintenance of adequate
urine flow, avoidance of xs doses and limitation
of course to 5 or fewer consecutive days
 May result in temporary Zn depletion
Clin. Significance unknown
Analogs: calcium, zinc disodium salts
of diethyletriaminepentaacetic acid
(DPTA), pentetate
Decorporation of uranium and certain
transuranic radioisotopes
Plutonium, americium, curium (2004)
 DEFEROXAMINE
Streptomyces pilosus
binds Fe avidly but binds
essential trace metals
poorly
Competes for loosely
bound Fe in transport
CHONs (hemosiderin and
ferritin), though fails to
compete for biologically
chelated Fe (microsomal
cytochromes and
hemoCHONs)
 Parenteral chelator of choice for Fe poisoning
+hemodialysis : tx for Al toxicity in renal
failure
Poorly absorbed orally, may inc Fe absorbtion
IM or IV
Metabolized, pathway unknown
Excreted in urine: orange red
Rapid IVHPN
Adverse idiosyncratic responses
Flushing, abdominal discomfort, rash
Pulmonary complications: ARDS in infusions >24h
Neurotoxicity
Inc susceptibility to certain infx! (Y. enterocolitica)
 DEFERASIROX
Tridentate chelator
High affinity for Fe, low for other metals
(Zn, Cu)
Orally active and well absorbed
in circu: binds Fe
excreted in the bile
Recently approved for oral tx of Fe
overload by blood transfusions
Thalassemia & myelodysplastic syndrome
THANK YOU!