A28: Antidotes in Depth

INTRODUCTION

Poisoning with salts of thallium or cesium are uncommon causes of life-threatening toxicity where supportive care may be insufficient to alter outcome. Radioactive cesium can be released as part of a nuclear incident or dispersed as a “dirty bomb,” producing radiation poisoning with sub-toxic cesium doses. Prussian blue is an orally available cation exchange resin that definitively enhances elimination of thallium and cesium in humans and animals and improves survivability in animals.

HISTORY

Prussian blue, the first artificially synthesized pigment, was discovered unintentionally by Diesbach in 1704 while attempting to make another ­pigment, cochineal red lake. Although immediately popular in art and later in printing, it took approximately 250 years to recognize that Prussian blue could attract monovalent alkali metals into its crystal lattice. Subsequently, in 1963, Nigrovic demonstrated that Prussian blue enhanced cesium elimination from the gastrointestinal tract of rats given either oral or intraperitoneal cesium.³⁷ In 2003, the US Food and Drug Administration (FDA) approved Prussian blue (Radiogardase) for the treatment of thallium and radioactive cesium poisoning.

The Prussian blue literature is complicated by many confusing chemical and physical terms. The product synthesized by Diesbach, Fe₄[Fe(CN₆)]₃, commonly known as insoluble Prussian blue, is assigned the Chemical Abstracts Service (CAS) number 14038-43-8 and is the FDA-approved product Radiogardase (Fig. A28–1). Synonyms for Prussian blue include Berlin blue, Hamburg blue, mineral blue, Paris blue, and Pigment blue 27, among others.⁵⁶ These names are often used interchangeably to refer to both insoluble Prussian blue and a soluble (colloidal) Prussian blue that either has the molecular formula KFe[Fe(CN)₆]₃ or K₃Fe[Fe(CN)₆]₃. Thus “Prussian blue” also carries two additional CAS numbers: 25869-98-1 and 12240-15-2.³⁸ Compounds containing the same basic core structure, such as NH₄Fe[Fe(CN)₆]₃ (ammonium ferric ferrocyanide or Chinese blue) and sodium ferric ferrocyanide, may have similar efficacy in binding monovalent cations and are also sometimes incorrectly called Prussian blue. For the purpose of clarity, general statements that follow use the term “Prussian blue.” In many instances the terms “insoluble” and “soluble” are chosen to highlight differences between the compounds. Unfortunately, because many studies do not specify which Prussian blue is used, some inherent ambiguity persists in the literature. Radiogardase, the currently available pharmaceutical preparation, is the insoluble form of Prussian blue, possibly selected preferentially for its efficacy in cesium poisoning.

PHARMACOLOGY

The crystal ...