117: Strychnine

HISTORY AND EPIDEMIOLOGY

Strychnine alkaloid occurs naturally in Strychnos nux-vomica, a tree native to tropical Asia and North Australia, and in Strychnos ignatii and Strychnos tiente, trees native to South Asia. The alkaloid was first isolated in 1818 by Pelletier and Caventou.^5,15 It is an odorless and colorless crystalline powder that has a bitter taste when dissolved in water. Besides strychnine, the dried seeds of S. nux-vomica contain brucine, a structurally similar, although less potent, alkaloid.⁸⁸ Strychnine is available from commercial sources in its salt form, usually as nitrate, sulfate, or phosphate.

Strychnine was first introduced as a rodenticide in 1540, and in subsequent centuries was used medically as a cardiac, respiratory, and digestive stimulant,⁴⁵ as an analeptic,⁹² and as an antidote to barbiturate⁹¹ and opioid overdoses.⁵⁹ Nonketotic hyperglycemia,^9,36,80 sleep apnea,⁷⁶ and snake bites¹⁵ were also once considered indications for strychnine use. In 1982, at least 172 commercial products were found to contain strychnine, including 77 rodenticides, 25 veterinary products, and 41 products made for human use.⁸³ However, the use of strychnine was substantially decreased; some countries such as the European Union banned its use as a rodenticide in 2006, and most of its prior medicinal indications are no longer utilized. Currently, strychnine is used as a rodenticide (for moles, gophers, and pigeons) and a research tool for the study of glycine receptors. Most commercially available strychnine-containing products contain about 0.25% to 0.5% strychnine by weight.⁸³

Between 1926 and 1928, strychnine killed more than three Americans every week.^5,27 In 1932, it was the most common cause of lethal poisoning in children,^5,83,98 and one-third of the unintentional poison-related deaths in children younger than 5 years were attributed to strychnine.⁶⁰ Currently, strychnine poisoning is rare and continues to decrease in the United States, although deaths are still reported. The Toxic Exposure Surveillance System (TESS) and National Poison Data System (NPDS) data of the American Association of Poison Control Centers (AAPCC) reported 1414 strychnine exposures during the past 10 years (2002–2011), with only eight deaths (Chap. 136).

Strychnine poisoning has resulted from deliberate exposure with suicidal and homicidal intent,^27,50 as well as from unintentional poisoning by a Chinese herbal medicine (Maqianzi)¹⁶ and a Cambodian traditional remedy (slang nut).^47,49,51,86 Maqianzi is used to treat limb paralysis, severe rheumatism, and inflammatory disease, whereas slang nut is used to treat gastrointestinal illness. The bitter taste of strychnine allows it to be used to adulterate heroin⁴³ and cocaine.^13,22,64 There are also reports of strychnine poisoning from adulterated amphetamines,²²3,4-methylenedioxymethamphetamine (MDMA),²⁵ Spanish fly,¹² and from the ingestion of gopher bait.⁵²

TOXICOKINETICS