The combination of sodium thiosulfate and sodium nitrite has been used in the United States since the 1930s as the primary antidote for cyanide intoxication. Although this combination was shown to exhibit much greater efficacy than either ingredient alone, the two compounds could not be used prophylactically because each exhibits a number of side effects. This review discusses the pharmacodynamics, pharmacokinetics, and toxicology of the individual agents, and their combination.

Cyanide is a toxic chemical that may be introduced into living organisms as a result of natural processes and/or anthropogenic uses (legal or illicit). Exposure to cyanide can be verified by analysis of cyanide or one of its breakdown products from biological samples. This verification may be important for medical, law-enforcement, military, forensic, research, or veterinary purposes. This review will discuss current bioanalytical techniques used for the verification of cyanide exposure, identify common problems associated with the analysis of cyanide and its biological breakdown products, and briefly address the metabolism and toxicokinetics of cyanide and its breakdown products in biological systems.

This toxicology update reviews the oxidative stress metabolites of catecholamines, postulated to be the biochemical initiators of cardiotoxicity. A brief overview of catecholamine metabolism is provided with several noteworthy historical observations relating to the autoxidation and rearrangement of epinephrine. The basic chemical and physical properties of adrenochrome and adrenolutin are discussed. The autoxidative, enzymatic and cellular basis for the transformation of catecholamines to oxidative metabolites is reviewed. Mechanisms seeking to account for the observed cardiotoxic changes in isolated heart perfusion studies and in vivo models are described.

Anisodamine is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in the People's Republic of China. Like atropine and scopolamine, anisodamine is a non-specific cholinergic antagonist exhibiting the usual spectrum of pharmacological effects of this drug class. It appears to be less potent and less toxic than atropine and displays less CNS toxicity than scopolamine. Anisodamine has been shown to interact with and disrupt liposome structure which may reflect its effects on cellular membranes. Experimental evidence implicates anisodamine as an anti-oxidant that may protect against free radical-induced cellular damage. Its cardiovascular properties include depression of cardiac conduction and the ability to protect against arrhythmia induced by various agents. Anisodamine is a relatively weak alpha(1) adrenergic antagonist which may explain its vasodilating activity. Its anti-thrombotic activity may be a result of inhibition of thromboxane synthesis. The T(1/2) of anisodamine in humans is about 2-3 h. Numerous therapeutic uses of anisodamine have been proposed including treatment of septic shock, various circulatory disorders, organophosphorus (OP) poisoning, migraine, gastric ulcers, gastrointestinal colic, acute glomerular nephritis, eclampsia, respiratory diseases, rheumatoid arthritis, obstructive jaundice, opiate addiction, snake bite and radiation damage protection. The primary therapeutic use of anisodamine has been for the treatment of septic shock. Several mechanisms have been proposed to explain its beneficial effect though most mechanisms are based upon the assumption that anisodamine ultimately acts by an improvement of blood flow in the microcirculation. Preliminary studies suggest another important therapeutic use of anisodamine is for the treatment of OP poisoning. Additional research is needed to delineate further the clinical usefulness of anisodamine relative to other anti-muscarinic drugs such as atropine and scopolamine.

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information AbstractThe cyanide metabolite 2-aminothiazoline-4-carboxylic acid (ATCA) is a promising biomarker for cyanide exposure because of its stability and the limitations of direct determination of cyanide and more abundant cyanide metabolites. A simple, sensitive, and specific method based on derivatization and subsequent gas chromatography-mass spectrometry (GC-MS) analysis was developed for the identification and quantification of ATCA in synthetic urine and swine plasma. The urine and plasma samples were spiked with an internal standard (ATCA-d 2 ), diluted, and acidified. The resulting solution was subjected to solid phase extraction on a mixed-mode cation exchange column. After elution and evaporation of the solvent, a silylating agent was used to derivatize the ATCA. Quantification of the derivatized ATCA was accomplished on a gas chromatograph with a mass selective detector. The current method produced a coefficient of variation of less than 6% (intra-and interassay) for two sets of quality control (QC) standards and a detection limit of 25 ng/ml. The applicability of the method was evaluated by determination of elevated levels of ATCA in human urine of smokers in relation to non-smokers for both males and females.