65: Cardioactive Steroids

HISTORY AND EPIDEMIOLOGY

The Ebers Papyrus provides evidence that the Egyptians used plants containing cardioactive steroids (CASs) at least 3000 years ago. However, it was not until 1785, when William Withering wrote the first systemic account about the effects of the foxglove plant, that the use of CASs was more widely accepted into the Western apothecary. Foxglove, the most common source of plant CAS, was initially used as a diuretic and for the treatment of “dropsy” (edema), and Withering eloquently described its “power over the motion of the heart, to a degree yet unobserved in any other medicine.”¹²⁴

Subsequently, CASs became the mainstay of treatment for congestive heart failure and to control the ventricular response rate in atrial tachydysrhythmias. Because of their narrow therapeutic index and widespread use, both acute and chronic toxicities remain important problems.⁸⁴ According to the American Association of Poison Control Centers data, between the years 2006 and 2011, there were approximately 8000 exposures to CAS-containing plants with one attributable deaths and about 14,500 exposures to CAS-containing xenobiotics resulting in more than100 deaths (Chap. 136).

Pharmaceutically induced CAS toxicity is typically encountered in the United States from digoxin; other internationally available but much less commonly used preparations are digitoxin, ouabain, lanatoside C, deslanoside, and gitalin. Digoxin toxicity most commonly occurs in patients at the extremes of age or those with chronic kidney disease (CKD). In children, most acute overdoses are unintentional by mistakenly ingesting an adult’s medication, or iatrogenic resulting from decimal point dosing errors (digoxin is prescribed in submilligrams, inviting 10-fold dosing calculation errors), or the elderly who are at risk for digoxin toxicity, most commonly from interactions with another medication in their chronic regimen or indirectly as a consequence of an alteration in the absorption or elimination kinetics. These include drug–drug interactions from an adult’s polypharmacy or from additional acute care xenobiotics that change CAS clearance in the liver or kidney, may alter protein binding and may result in increased bioavailability.

CAS toxicity may also result from exposure to certain plants or animals, including oleander (Nerium oleander), yellow oleander (Thevetia peruviana), which has been implicated in the suicidal deaths of thousands of patients in Southeast Asia,²⁶ foxglove (Digitalis spp), lily of the valley (Convallaria majalis), dogbane (Apocynum cannabinum), and red squill (Urginea maritima). CAS poisoning may result from teas containing seeds of these plants and water and herbal products contaminated with plant CASs (Chap. 45).^{16,19,52,79,90,97,116} Toxicity has resulted from ingestion, instead of the intended topical application, of a purported aphrodisiac derived from the dried secretion of toads from the Bufo species, which contains a bufadienolide-class CAS.^10,12,13 Although there have been no reported human exposures, fireflies of the Photinus species (...