Chemistry Reference
In-Depth Information
muscularly at a rate of 2 g for an adult and 1 g for a child
every 12 hours. Gastric lavage may be performed with
5 g desferrioxamine dissolved in 1 liter of water, and
5-10 g desferrioxamine in 50-100 mL water may be left
in the stomach to chelate unabsorbed iron from the gut.
While being well tolerated, the rapid intravenous
administration of desferrioxamine may cause transient
hypotension with histamine-like or anaphylactic reac-
tions. The drug should be used cautiously in patients
with impaired renal function.
3.5.9 Combinations of Chelating Agents
Combined treatment with EDTA and dimercaprol
is most effective in acute lead poisoning in children
with encephalopathy or blood lead levels greater than
100
mol/L), showing greater
therapeutic effectiveness than EDTA alone. The reason
for this is thought to be related to synergistic action
of EDTA, which may intensify the inhibitory action of
lead on hemosynthesis by a similar action on
µ
g/dL (1000
µ
g/L; 5
µ
-ami-
nolevulinic acid dehydrogenase. With intravenous
EDTA infusion, to prevent a transfer of chelated lead to
the brain, intravenous administration of dimercaprol
should be given 4 hours before and continued during
EDTA treatment (Grisemer, 2001).
The possible therapeutic advantages of using combi-
nations of chelating agents, with particular reference to
aiding the elimination of cadmium and plutonium, are
considered by Schubert (1983). Experimental observa-
tions in mice dosed with cadmium chloride indicated
an additive protective effect using the two chelators
DTPA and DMPS. Chelator combinations tested for
their effectiveness in the elimination of plutonium
have included DTPA with desferrioxamine and EDTA
together with a number of bidentate ligands. EDTA with
bidentate ligands such as
p
-aminosalicylic acid signifi -
cantly reduced the plutonium content in mouse liver
and bone.
The rationale in using two different complexing
agents to produce a synergistic effect is that the fi rst
agent should be suffi ciently lipophilic to mobilize the
metal from intracellular binding sites and promote its
release into the blood, whereas the second agent will
promote ligand exchange to form an ionized chelate
that can then be excreted into the urine.
δ
3.5.6 Deferiprone (L1)
Deferiprone, 1, 2-dimethyl-3-hydroxypyrid-4-one, is
effective for long-term iron chelation therapy of trans-
fusional iron overload in thalassemia. Given by mouth,
it is suitable for home treatment (Kontoghiorges
et al
.,
2000). Deferiprone together with desferrioxamine in
lower doses is indicated in cases requiring lifelong che-
lation (Mourad
et al
., 2003).
3.5.7 Diethylenetriaminepentaacetic Acid (DTPA)
DTPA is another synthetic polyaminopolycarbox-
ylic acid with properties similar to those of EDTA,
which also forms stable chelates with calcium. The cal-
cium salt has been used to accelerate the elimination
of plutonium and related actinide metals. Because zinc
depletion may occur during long-term administration,
it has been suggested that the more effective calcium
DTPA be replaced by zinc DTPA in the later stages of
treatment (Taylor and Volf, 1980). As with all chela-
tors, DTPA is most effective if administered shortly
after exposure. Lipophilic derivatives of DTPA are
being developed, as, for example, Puchel, which can
be administered as an aerosol to decrease the lung con-
centration of inhaled insoluble plutonium oxide parti-
cles (Stradling
et al
., 1981). Small amounts of plutonium
and americium have been successfully eliminated with
DTPA given in a dose range of about 1 g/day or about
30 mIU mol/kg body weight, in a few cases for long
periods without adverse effect (Bair and Thompson,
1974; Taylor, 1982).
3.6 Modifi cation of Response
Under this heading are included examples of thera-
peutic measures in metal poisoning that are directed
toward a modifi cation of the tissue response to the poi-
son or to an alteration in the biochemical or metabolic
state of the subject.
3.5.8 Diethyldithiocarbamate (DEDTC)
3.6.1 Modifi cation of Tissue Response
DEDTC is a chelating agent that has been found to be
of value in the treatment of acute nickel carbonyl poison-
ing, greatly increasing the excretion of nickel in the urine
(Sunderman, 1971). DEDTC can be given orally in mod-
erately severe poisoning, initially at a rate of 50 mg/kg
in divided doses. At the low pH of gastric juice, DEDTC
is degraded to ethylamine and carbon disulfi de. This
reaction can be minimized by the concomitant adminis-
tration of 2 g sodium bicarbonate by mouth.
Chronic beryllium disease is characterized by
an infl ammatory reaction that is granulomatous in
nature and that seems to result from a hypersensi-
tive response in certain individuals. The infl amma-
tory process may be arrested, although not reversed,
by adequate corticosteroid therapy. This treatment has
resulted in a change in the clinical course of the disease
with a reduction in symptoms and a favorable change
in prognosis.
