DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1864
BLOOD LEAD (μg/dL)
Children Adults
150
death
encephalopathy
neuropathy
frank anemia
colic
hemoglobin
urinary coproporphyrin and δ-ALA
nerve conduction velocity
vitamin D metabolism
100
50
40
30
20
encephalopathy
frank anemia
longevity
hemoglobin synthesis
peripheral neuropathies
infertility (men)
nephropathy
urinary coproporphyrins and δ-ALA
systolic blood pressure (men)
hearing acuity
erythrocyte protoporphyrin (men)
SECTION IX
SPECIAL SYSTEMS PHARMACOLOGY
erythrocyte protoporphyrin
neural development
sign of high-level exposure to the metal. The abdominal
syndrome often begins with a persistent metallic taste,
mild anorexia, muscle discomfort, malaise, headache, and
usually constipation. Occasionally, diarrhea replaces constipation.
As intoxication advances, symptoms worsen
and include intestinal spasms that cause severe intestinal
pain (lead cholic). Intravenous calcium gluconate can
relieve this pain.
Carcinogenesis. IARC recently upgraded lead to “probably
carcinogenic to humans” (group 2A; IARC, 2006).
Epidemiological studies have shown associations
between lead exposure and cancers of the lung, brain,
kidney, and stomach. Rodents exposed to lead develop
kidney tumors, and some rats develop gliomas. Lead is
not mutagenic but increases clastogenic events. The
mechanism of lead carcinogenesis is unknown but may
result from inhibition of DNA binding zinc-finger proteins,
including those involved in DNA repair and synthesis
(Silbergeld, 2003). Lead is a good example of a
non-genotoxic carcinogen.
Treatment. The most important response to lead poisoning
is removal of the source of lead exposure.
Supportive measures should be undertaken to relieve
symptoms.
Chelation therapy is warranted for children and adults with
high blood lead levels (>45 μg/dL and >70 μg/dL, respectively)
10
1
erythrocyte protoporphyrin (women)
decrease
increase
Figure 67–5. Manifestations of lead toxicity associated with varying concentrations of lead in the blood of children and adults.
-ALA, -aminolevulinate.
and/or acute symptoms of lead poisoning (Ibrahim et al., 2006).
Although chelation therapy is effective at lowering blood lead
levels and relieving immediate symptoms, it does not reduce the
chronic effects of lead beyond the benefit of lead abatement alone
(Rogan et al., 2001). In rats, chelators enhance mobilization of
lead from the soft tissues to the brain and may increase the
adverse neurodevelopmental effects of lead (Andersen and
Aaseth, 2002).
Mercury
Mercury is a unique metal in that it is a liquid at room
temperature. Because of its capacity to amalgamate
with other metals, mercury has been used industrially
since ancient Greece, and mercury’s toxicity was noted
by Hippocrates. Mercury also was used as a therapeutic
drug for several centuries. Indeed, its use for the
treatment of syphilis inspired Paracelsus’ observation
that “the dose makes the poison,” one of the central
concepts of toxicology, and also gave rise to the cautionary
expression, “A night with Venus, a year with
Mercury.” Toxicities from occupational exposure to
mercury have been known for a long time. For instance,
the phrase “mad as a hatter” originated from the exposure
of hatters to metallic mercury vapor during production
of felt for hats using mercury nitrate (Goldwater,
1972). While the phrase likely inspired the character of
the Mad Hatter in Alice in Wonderland, his symptoms
are not consistent with mercury exposure.