36: Colchicine, Podophyllin, and the Vinca Alkaloids

COLCHICINE

History

The origins of colchicine and its history in poisoning can be traced to Greek mythology. Medea was the evil daughter (and a known poisoner) of the king of Colchis, a country that lay east of the Black Sea in Asia Minor. After being betrayed by her husband Jason (of Jason and the Argonauts), she killed their children and her husband’s lover. Medea is often used plants of the Liliaceae family to poison her victims, one of which is Colchicum autumnale.^25,144,192 The use of colchicum for medicinal purposes is reported in Pedanius Dioscorides De Materia Medica, an ancient medical text, written in the 1st century a.d.^25,144,192 and subsequently in the 6th century a.d. by Alexander of Trallis, who recommended it for arthritic conditions.^{25,40,181,192,176} However, colchicum fell out of favor, perhaps because of its pronounced gastrointestinal (GI) effects, until it was reintroduced for dropsy and various other nonrheumatic conditions in 1763.^25,192 In the late 18th century, a colchicum containing product known as Eau Medicinale reportedly had strong antigout effects.¹⁹² Colchicine, the active alkaloidal component in colchicum, was isolated in 1820 and rapidly became popular as an antigout medication.^144,192 Benjamin Franklin reportedly had gout and is credited with introducing colchicine in the United States.¹⁴⁴ Colchicine is still used in the treatment of gout and has been used in a multitude of other disorders, including amyloidosis, Behçet syndrome, familial Mediterranean fever, chronic pericarditis, arthritis, pulmonary fibrosis, vasculitis, biliary cirrhosis, microcrystalline arthritis, certain spondyloarthropathies, calcinosis, and scleroderma.^{12,25,133,137} Unfortunately, systematic data supporting the efficacy of colchicine therapy in many of these other diseases are lacking.

Colchicine is derived from two plants of the Liliaceae family, C. autumnale (autumn crocus, meadow saffron, wild saffron, naked lady, son-before-the-father) and Gloriosa superba (glory lily).¹⁹² Colchicine is not distributed evenly in the autumn crocus with the highest concentrations found in the bulb and seeds (0.8%) followed by the corm or underground stem (0.6%) and the flowers (0.1%).^144,169,181 Colchicine concentrations within the plant peak during the summer months.¹⁴⁴ The leaves of C. autumnale closely resemble those of the Allium ursinum or wild garlic and have been mistaken for them.^44,45,110 The tubers of G. superba may be confused with Ipomoea batatas (sweet potatoes).¹⁹²

There is a dearth of epidemiologic data on colchicine poisoning. The American Association of Poison Control Centers records several hundred overall exposures annually (Chap. 136). Most of these exposures are in adults and are categorized as unintentional. Approximately 10% of the cases with a recorded outcome typically have evidence of moderate or major toxicity or resulted in death.⁴¹ Although a limited number ...