Dimercaprol
BAL; British Anti-Lewisite: Dimercaprolum.
Pharmocopoeias.
A clear colourless or slightly yellow liquid with an alliaceous
odour. Soluble in water and in arachis oil: miscible with alco
hol, benzyl benzoate, and methyl alcohol. Store at 2Β° to 8Β°
Adverse Effects and Treatment
The most consistent side-effects produced by dimer
caprol are hypertension and tachycardia. Other side
effects include nausea, vomiting, headache, burning
sensation of the lips, mouth, throat, and eyes, lach
arymation and salivation, tingling of the extremities,
a sensation of constriction in the throat and chest,
muscle pains and muscle spasm, rhinorrhoea, con
junctivitis, sweating, restlessness, and abdominal
pain. Transient reductions in the leucocyte count
have also been reported. Pain may occur at the injection
site and sterile abscesses occasionally develop.
In children, fever commonly occurs and persists
During therapy.
Side-effects are dose-related, relatively frequent.
and usually reversible. It has been suggested that
oral administration of ephedrine sulphate 30 to
60 mg half an hour before each injection of dimere-
aprol may reduce side-effects, antihistamines may
alleviate some of the symptoms.
Precautions
Dimercaprol should be used with care in patients
with hypertension or impaired renal function. It
should be discontinued or continued with extreme
caution if acute renal insufficiency develops during
therapy. Alkalinisation of the urine may protect the
kidney during therapy by stabilising the dimerc-
aprol-metal complex. Dimercaprol should not be
used in patients with impaired hepatic function un-
less due to arsenic poisoning. It should not be used
in the treatment of poisoning due to cadmium, iron.
or selenium as the dimereaprol-melal complexes
formed are more toxic than the metals themselves.
Glucose-6-phosphate dehydrogenue deficiency. A
report' of haemolysis during chelation therapy with dimerc-
aprol and sodium calcium edetate for high blood-lead concen-
trations in 2 children with a deficiency of glucosc-6-
phosphate dehydrogenase.
Pharmacokinetics
After intramuscular injection, maximum blood con-
centrations of dimercaprol may be attained within
30 to 60 minutes. Dimercaprol is rapidly metabo-
lised and the metabolites and dimercaprol-metal
chelates are excreted in the urine and bile. Elimina-
tion is essentially complete within 4 hours of a sin-
gle dose.
Uses and Administration
Dimercaprol is a chelator used in the treatment of
acute poisoning by arsenic, gold, and mercury: its role in the treatment of
poisoning by antimony, bismuth, and thallium is less
well established. It is also used, in conjunction with
sodium calciumedetate, in acute lead poisoning.
The sulfhydryl groups on dimercaprol compete with
endogenous sulfhydryl groups on proteins such as
enzymes to combine with these metals; chelation by
dimercaprol therefore prevents or reverses any inhi-
bition of the sulfhydryl enzymes by the metal and
the dimercaprol-metal complex formed is readily
excreted by the kidney. Since the complex may dis-
sociate. particularly at acid pH, or be oxidised, the
aim of treatment is to provide an excess of dimerc-
aprol in body fluids until the excretion of the metal
is complete.
Dimercaprol should be administered by deep intra-
muscular injection and the injections should be giv-
en at different sites. Various dosage schedules are in
use.
In the UK a recommended schedule for adults is to
give doses of 400 to 800 mg on the first day of treat
ment, 200 to 400 mg on the second and third day:
and 100 to 200 mg on the fourth and subsequent
days, all administered in divided doses. Within these
dose ranges, the individual dose is determined by
body-weight, severity of symptoms, and the causa
tive agent. Single doses should not generally exceed
3 mg per kg body-weight but single doses of up to
5 mg per kg may be required initially in patients
with severe acute poisoning. The dose for children
based on body-weight using a similar dose per kg.
for adults. A minimum interval of 4 hours between
doses appears to reduce side-effects.
In the USA a recommended schedule for severe a-
rsenical or gold poisoning is 3 mg per kg body
weight given at 4-hourly intervals' throughout the
first 2 days, 4 doses are given on the third day, and
2 doses on each of the next 10 days. In milder cases
2.5 mg per kg is given 4 times daily on each of the
first 2 days, twice daily on the third day, and once
daily on subsequent days for 10 days. For acute mer-
curial poisoning an initial injection of 5 mg per kg is
followed by 2.5 mg per kg once or twice daily for 10
days.
Some authorities have suggested that doses of up to
5 mg per kg every 4 hours may be required during
the first I or 2 days of treatment in severe poisoning
with gold, mercury, or arsenic.
Dimercaprol is also used in conjunction with sodi-
um calcium edetate in the treatment of lead
poisoning. It can be of particular value in the treat-
ment of acute lead encephalopathy and a suggested
procedure is to administer an initial dose of dimerc-
aprol 4 mg per kg alone followed at 4-hourly inter-
vals by dimercaprol 3 to 4 mg per kg with
concomitant doses of sodium calciumedetate ad-
ministered at a separate site; treatment may be maintained for 2 to 7 days depending on the clinical response.