Page 1042 - Basic _ Clinical Pharmacology ( PDFDrive )

1028 SECTION IX Toxicology

lamps, pesticides, biocides and antiseptics, measuring instruments B. Chronic
(eg, thermometers, sphygmomanometers), and manufacturing Chronic poisoning from inhalation of mercury vapor results
processes such as chloralkali production (by 2025) in a classic triad of tremor, neuropsychiatric disturbance, and
gingivostomatitis. The tremor usually begins as a fine intention
Pharmacokinetics tremor of the hands, but the face may also be involved, and pro-
gression to choreiform movements of the limbs may occur. Neu-
The absorption of mercury varies considerably depending on the ropsychiatric manifestations, including memory loss, fatigue,
chemical form of the metal. Elemental mercury is quite volatile insomnia, and anorexia, are common. There may be an insidious
and can be absorbed from the lungs (Table 57–1). It is poorly change in mood to shyness, withdrawal, and depression along
absorbed from the intact gastrointestinal tract. Inhaled mercury is with explosive anger or blushing (a behavioral pattern referred
the primary source of occupational exposure. Organic short-chain to as erethism). Recent studies suggest that low-dose exposure
alkylmercury compounds are volatile and potentially harmful by may produce subclinical neurologic effects. Gingivostomatitis,
inhalation as well as by ingestion. Percutaneous absorption of sometimes accompanied by loosening of the teeth, may be
metallic mercury and inorganic mercury can be of clinical concern reported after high-dose exposure. Evidence of peripheral nerve
following massive acute or long-term chronic exposure. Alkylmer- damage may be detected on electrodiagnostic testing, but overt
cury compounds appear to be well absorbed through the skin, and peripheral neuropathy is rare. Acrodynia is an uncommon idio-
acute contact with a few drops of dimethylmercury has resulted in syncratic reaction to subacute or chronic mercury exposure and
severe, delayed toxicity. After absorption, mercury is distributed occurs mainly in children. It is characterized by painful erythema
to the tissues within a few hours, with the highest concentration of the extremities and may be associated with hypertension, dia-
occurring in the kidney. Inorganic mercury is excreted through the phoresis, anorexia, insomnia, irritability or apathy, and a miliary
urine and feces. Excretion of inorganic mercury follows a multi- rash. Chronic exposure to inorganic mercury salts, sometimes via
compartment model: most is excreted within weeks to months, topical application in cosmetic skin-lightening creams, has been
but a fraction may be retained in the kidneys and brain for years. associated with neurological symptoms and renal toxicity in case
After inhalation of elemental mercury vapor, urinary mercury reports and case series.
levels decline with a half-life of approximately 1–3 months. Methylmercury intoxication affects mainly the CNS and
Urine mercury concentration is <3 mcg/L in most individuals results in paresthesias, ataxia, hearing impairment, dysarthria, and
without occupational exposure, and the median general popula- progressive constriction of the visual fields. Signs and symptoms
tion urine mercury concentration in the 2011–2012 NHANES of methylmercury intoxication may first appear several weeks
was 0.324 mcg/L. Methylmercury, which has a blood and whole- or months after exposure begins. Methylmercury is a reproduc-
body half-life of approximately 50 days, undergoes biliary excre- tive toxin. High-dose prenatal exposure to methylmercury may
tion and enterohepatic circulation, with more than two thirds produce mental retardation and a cerebral palsy-like syndrome
eventually excreted in the feces. The geometric mean total blood in the offspring. Low-level prenatal exposures to methylmercury
mercury concentration in the US population in the 2011–2012 have been associated with a risk of subclinical neurodevelopmental
NHANES was 0.703 mcg/L; the 95th percentile was 4.40 mcg/L deficits.
(~90% present as methylmercury). Mercury binds to sulfhydryl A 2004 report by the Institute of Medicine’s Immunization
groups in keratinized tissue, and as with lead and arsenic, traces Safety Review Committee concluded that available evidence
appear in the hair and nails. Mercury in hair has served as a valid favored rejection of a causal relation between thimerosal-containing
biomarker of methylmercury exposure over an interval of weeks to vaccines and autism. In like manner, a recent retrospective cohort
months in epidemiologic studies. study conducted by the CDC did not support a causal association
between early prenatal or postnatal exposure to mercury from
Major Forms of Mercury Intoxication thimerosal-containing vaccines and neuropsychological function-
ing later in childhood.
Mercury interacts with sulfhydryl groups in vivo, inhibiting Dimethylmercury is a rarely encountered but extremely neu-
enzymes and altering cell membranes. The pattern of clinical rotoxic form of organomercury that may be lethal in small
intoxication from mercury depends to a great extent on the quantities.
chemical form of the metal and the route and severity of exposure. The diagnosis of mercury intoxication involves integration of
the history and physical findings with confirmatory laboratory test-
A. Acute ing or other evidence of exposure. In the absence of occupational
Acute inhalation of elemental mercury vapors may cause exposure, the urine mercury concentration is usually <5 mcg/L,
chemical pneumonitis and noncardiogenic pulmonary edema. and whole blood mercury is <5 mcg/L. In 1990, the Biological
Acute gingivostomatitis may occur, and neurologic sequelae Exposure Index (BEI) Committee of the American Conference
(see following text) may also ensue. Acute ingestion of inor- of Governmental Industrial Hygienists (ACGIH) recommended
ganic mercury salts, such as mercuric chloride, can result in a that workplace exposures should result in urinary mercury con-
corrosive, potentially life-threatening hemorrhagic gastroenteri- centrations <35 mcg per gram of creatinine and end-of-work-week
tis followed within hours to days by acute tubular necrosis and whole blood mercury concentrations <15 mcg/L. To minimize the
oliguric renal failure. risk of developmental neurotoxicity from methylmercury, the EPA