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Chapter: Basic & Clinical Pharmacology : Heavy Metal Intoxication & Chelators

Prussian Blue (Ferric Hexacyanoferrate)

Ferric hexacyanoferrate (insoluble Prussian blue) is a hydrated crystalline compound in which Fe2+ and Fe3+atoms are coordi-nated with cyanide groups in a cubic lattice structure.

PRUSSIAN BLUE (FERRIC HEXACYANOFERRATE)

Ferric hexacyanoferrate (insoluble Prussian blue) is a hydrated crystalline compound in which Fe2+ and Fe3+atoms are coordi-nated with cyanide groups in a cubic lattice structure. Although used as a dark blue commercial pigment for nearly 300 years, it was only three decades ago that its potential usefulness as a phar-maceutical chelator was recognized. Primarily by ion exchange, and secondarily by mechanical trapping or adsorption, the com-pound has high affinity for certain univalent cations, particularly cesium and thallium. Used as an oral drug, insoluble Prussian blue undergoes minimal gastrointestinal absorption (< 1%). Because the complexes it forms with cesium or thallium are nonabsorb-able, oral administration of the chelator diminishes intestinal absorption or interrupts enterohepatic and enteroenteric circula-tion of these cations, thereby accelerating their elimination in the feces. In clinical case series, the use of Prussian blue has been asso-ciated with a decline in the biologic half-life (ie, in vivo retention) of radioactive cesium and thallium.

Indications & Toxicity

In 2003, the FDA approved Prussian blue for the treatment of contamination with radioactive cesium (137Cs) and intoxication with thallium salts. Approval was prompted by concern over potential widespread human contamination with radioactive cesium caused by terrorist use of a radioactive dispersal device (“dirty bomb”). The drug is part of the Strategic National Stockpile of pharmaceuticals and medical material maintained by the CDC (http://www.bt.cdc.gov/stockpile/#material). (Note: Although soluble forms of Prussian blue, such as potassium ferric hexacyanoferrate, may have better utility in thallium poi-soning, only the insoluble form is currently available as a phar-maceutical.)

After exposure to 137Cs or thallium salts, the approved adult dosage is 3 g orally three times a day; the corresponding pediatric dosage (2–12 years of age) is 1 g orally three times a day. Serial monitoring of urine and fecal radioactivity (137Cs) and urinarythallium concentrations can guide the recommended duration of therapy. Adjunctive supportive care for possible acute radiation illness (137Cs) or systemic thallium toxicity should be instituted as needed.

Prussian blue has not been associated with significant adverse effects. Constipation, which may occur in some cases, should be treated with laxatives or increased dietary fiber.


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