Page 1034 - Basic _ Clinical Pharmacology ( PDFDrive )

57 Heavy Metal Intoxication
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& Chelators

Michael J. Kosnett, MD, MPH

C ASE STUD Y

Following Sunday morning services, 27 people attended a individuals were hospitalized with ongoing gastrointestinal
church social where coffee, baked goods, and sandwiches were symptoms, hypotension, and anion gap metabolic acidosis.
served. Within 15–60 minutes, 13 people developed vomiting Fluid resuscitation and pressors were accompanied by adequate
and abdominal discomfort, accompanied over the next several urine output. What diagnoses should be considered? What tests
hours by nonbloody diarrhea. Within 12 hours, seven of these should be conducted, and what therapy should be considered?

Some metals such as iron are essential for life, whereas others such of storage batteries (nearly 90% of US consumption), ammunition,
as lead are present in all organisms but serve no useful biologic metal alloys, solder, glass, plastics, pigments, and ceramics. Corro-
purpose. Some of the oldest diseases of humans can be traced to sion of lead plumbing in older buildings or supply lines may increase
heavy metal poisoning associated with metal mining, refining, and the lead concentration of tap water. Environmental lead exposure,
use. Even with the present recognition of the hazards of heavy ubiquitous by virtue of the anthropogenic distribution of lead to air,
metals, the incidence of intoxication remains significant, and the water, and food, has declined considerably in the last three decades
need for preventive strategies and effective therapy remains high. as a result of the elimination of lead as an additive in gasoline, as
Toxic heavy metals interfere with the function of essential cations, well as diminished contact with lead-based paint and other lead-
cause enzyme inhibition, generate oxidative stress, alter gene containing consumer products, such as lead solder in cans used as
expression, and perturb cell signaling. As a result, multisystem food containers. Legislation in the United States in 2011 further
signs and symptoms are a hallmark of heavy metal intoxication. reduced the maximum permissible lead content of children’s prod-
When intoxication occurs, chelator molecules (from chela ucts to 100 ppm. Lead continues to be used in some formulations of
“claw”), or their in vivo biotransformation products, may be used aviation gasoline for piston-engine aircraft. The presence of lead in
to bind the metal and facilitate its excretion from the body. Chela- certain folk medicines (eg, the Mexican remedies azarcon and greta,
tor drugs are discussed in the second part of this chapter. and certain Ayurvedic preparations) and in cosmetics (eg, kohl
utilized around the eyes in certain African and Asian communities)
■ TOXICOLOGY OF HEAVY has contributed to lead exposure to children and adults. Although
public health measures, together with improved workplace condi-
METALS tions, have decreased the incidence of serious overt lead poisoning,
there remains considerable concern over the effects of low-level
LEAD lead exposure. Extensive evidence indicates that low levels of lead
exposure may have subtle subclinical adverse effects on neurocogni-
Lead poisoning is one of the oldest occupational and environmental tive function in children and may contribute to hypertension and
diseases in the world. Despite its recognized hazards, lead continues cardiovascular disease in adults. Lead serves no useful purpose in
to have widespread commercial application, including production the human body. In key target organs such as the developing central

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