Chapter 34: Colchicine, Podophyllin, and the Vinca Alkaloids

INTRODUCTION

Colchicine, podophyllotoxin, and the vinca alkaloids exert their primary toxicity by binding to tubulin and interfering with microtubule structure and function. The ubiquitous nature of microtubules within human cells and the heavy reliance on them for maintenance of normal cell functions present numerous opportunities for these xenobiotics to cause dysfunction at a cellular, organ, and organ system level in a dose-dependent fashion. This chapter discusses the history, pharmacology, pharmacokinetics, toxicokinetics, pathophysiology, toxic dose, clinical manifestations, diagnostic testing and management of toxicity resulting from these xenobiotics both during therapeutic use and in the overdose setting. Because some information is limited, not all of the aforementioned topics will be discussed for each xenobiotic.

COLCHICINE

History

The origins of colchicine and its history in poisoning can be traced back 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 used plants of the Liliaceae family, of which Colchicum autumnale is a member, to poison her victims.^20,132,172 The use of colchicum for medicinal purposes is reported in Pedanius Dioscorides De Materia Medica, an ancient medical text, written in the first century A.D.,¹³² and subsequently in the 6th century A.D. by Alexander of Tralles, who recommended it for treating arthritic conditions.¹¹⁰ However, colchicum fell out of favor, perhaps because of its pronounced gastrointestinal (GI) effects, until it was introduced for “dropsy” and various other nonrheumatic conditions in 1763.^20,172 In the late 18th century, a colchicum-containing product known as Eau Medicinale appeared, which reportedly had strong antigout effects.¹⁷² Colchicine, the active alkaloidal component in colchicum, was isolated in 1820 and rapidly became popular as an antigout medication.^132,172 Benjamin Franklin reportedly had gout and is credited with introducing colchicine in the United States.¹³² Colchicine is still used in the acute treatment and prevention of gout and is used in other disorders, including amyloidosis, Behçet’s syndrome, familial Mediterranean fever, pericarditis, arthritis, pulmonary fibrosis, vasculitis, biliary cirrhosis, pseudogout, certain spondyloarthropathies, calcinosis, and scleroderma.^{11,20,121,125} 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).¹⁷² The autumn crocus contains different amounts of colchicine by weight, depending on the plant part (bulb, 0.8%; flowers, 0.1%; seeds, 0.8%; and the corm or underground stem, 0.6%).^110,132,151 Colchicine concentrations within the plant peak during the summer months.¹³² The leaves of C. autumnale closely resemble ...