Chemistry Reference
In-Depth Information
intracranial pressure, it has been advised to admin-
ister dimercaprol parenterally before calcium EDTA
(Griesemer, 2001). The half-life is short, metabolism
and excretion being complete within 4 hours.
Dimercaprol is given by deep intramuscular injec-
tion as a 5% solution in arachis oil BP (or a 10% solu-
tion with benzyl benzoate in vegetable oil, USP). It is
usually given in a dose of 2.5-3 mg/kg, every 4 hours,
for the fi rst 2 days, every 6 hours on the third day,
and thereafter once or twice daily for up to 10 days.
In a severe acute case of poisoning, 4-5 mg/kg may be
given, every 4 hours for the fi rst 24 hours, but no single
dose should exceed 300 mg. There are several variations
to this schedule. The drug should be administered at a
lower dosage to patients with impaired renal function.
It is wise to render the urine alkaline during therapy,
because the dimercaprol-metal complex may dissoci-
ate in an acidic medium.
Dimercaprol has unpleasant and sometimes alarm-
ing side effects when given in full dosage. One of the
most consistent is a rise in blood pressure accompa-
nied by tachycardia. Other untoward effects are nau-
sea and vomiting, headache, burning sensations in
the mouth and throat, with paresthesia of the hands, a
feeling of constriction or pain in the chest, lacrimation,
salivation, rhinorrhea, sweating, and abdominal pain
accompanied by a feeling of anxiety.
Dimercaprol has been shown in the experimental
animal to inhibit the blood pressure-lowering effect of
intravenously injected cadmium (Dalhamn and Friberg,
1954) and also of vanadium and cobalt. Although the
urinary excretion of cadmium is enhanced by dimerc-
aprol, Tepperman (1947) showed this to be accompa-
nied by a large increase in cadmium concentration in
the kidney, and Gilman
et al
. (1946) observed severe
renal damage as a sequel. Dimercaprol is, therefore,
contraindicated in cadmium poisoning.
The administration of dimercaprol in mercury poi-
soning effects a redistribution of the body burden of
the metal without increasing its excretion. In poisoning
with inorganic mercuric salts, dimercaprol decreases
the renal concentration and thus protects the kidney.
However, with phenylmercury and with alkylmercury
compounds, dimercaprol accelerates the uptake of
mercury from blood into the tissues and in particular
its uptake into the brain (Berlin and Lewander, 1965;
Berlin
et al
., 1965). Dimercaprol is, therefore, contraindi-
cated in the treatment of poisoning with both aryl- and
alkylmercury compounds. Dimercaprol enhances the
toxicity of selenium and tellurium, producing kidney
damage, and is contraindicated in poisoning by these
metals (Amdur, 1958; Cerwenka and Cooper, 1961).
Because of its high toxicity, dimercaprol is now
suited only for brief treatment of acute intoxications
(Andersen and Aaseth, 2002). DMPS and DMSA
have now superseded dimercaprol in most cases of
poisoning.
3.5.1.1 Sodium 2,3-Dimercaptopropane Sulfonate
(DMPS; Unithiol)
This water-soluble chemical analog of dimercaprol,
with dimercaptosuccinic acid (considered below), is
an effective antidote for certain forms of heavy metal
poisoning, less toxic than dimercaprol, which has been
used extensively in Russia and more recently in the
Western world.
Both agents increase the urinary excretion of copper
and zinc, but in therapeutic doses, this is not consid-
ered to be of clinical signifi cance. Allergic side effects
have been reported. The properties and uses of these
two chelating agents have been reviewed by Aposhian
(1983). DMPS is effective in accelerating metal excre-
tion without causing severe adverse health effects in
acute and chronic intoxication by organic and inor-
ganic mercury, bismuth, arsenic, and chronic lead poi-
soning (Andersen, 1999; Aposhian
et al
., 1995).
DMPS (unithiol) may be given orally or parenter-
ally. It has been given intramuscularly as a 5% solution
at the rate of 5 mg/kg three or four times during the
fi rst 24 hours, two or three times on the second day,
and once or twice on subsequent days.
DMPS has been given successfully in one case of
Wilson's disease where intolerance had developed
to penicillamine and to triethylene tetramine, result-
ing in effective cupruresis (Walshe, 1984, 1985). In
two other cases reported by the same author, adverse
effects were reported. In experimental animals, DMPS
has prevented the lethal effects of a number of arsenic
compounds, and it has been used in Eastern Europe
in the treatment of arsenic poisoning in man. Together
with dimercaprol it is, however, contraindicated in ars-
ine poisoning. DMPS has been used successfully in the
Soviet Union in the treatment of chronic lead poison-
ing. It is in the treatment of alkylmercury poisoning
that DMPS may have a major role. In a study of the
relative effectiveness of DMPS, a thiolated resin, and
the penicillamines, in the Iraqi outbreak of alkylmer-
cury poisoning, DMPS was the most effective agent,
reducing the mean T 1/2 value for mercury in blood
from about 65-10 days (Clarkson
et al
., 1981). Adverse
effects of treatment were not seen, and the authors
concluded that a reduction in blood mercury level
with accelerated excretion would be clinically useful if
given before irreversible damage had occurred. DMPS
has also been given in inorganic mercury poisoning
after the inhalation of mercury vapor and the ingestion
of mercuric oxide. It has been shown to be effective in
increasing mercury excretion in urine (Mant, 1985).
