Digitalis: The flower, the drug, the poison

This old drawing depicting Digitalis purpurea, from a book by Gera-Untermhaus, Franz Eugen Köhler in 1887, although it is signed W. Müller (Photo is in public domain because it was published before 1923)

Digitalis is a genus of twenty species of flowers that grow wild in much of the eastern hemisphere, and are widely planted as ornamentals by gardeners like me in the U.S. Several species have been used medically for centuries, and are still the source for digoxin, a drug still used to treat cardiac arrhythmia. The medical use of digitalis was popularized by a British physician, William Withering, whose book, An Account of the Foxglove, was first published in 1785. 

Withering's book contained as the frontispiece a drawing of the foxglove, or Digitalis purpurea, which has wide leaves with serrated edges and tall spikes bearing elongated bell-like purple flowers. Digitalis (finger-like) refers to the shape of the flowers. 

Withering advised to gather the leaves at about the time that blossoms are coming out. These were "dried, either in the sunshine or on a tin pan or pewter dish before a fire. If well dried, these rub down to a beautiful green powder." Withering used the powder directly or made an infusion from it.

The leaves today are extracted to yield digoxin, a cardiac glycoside, a complex molecule with multiple carbohydrate type rings. Digoxin appears to inhibit the Na+/K+ ATPase pump in cardiac muscle cells, leading to excess intracellular Na+, which indirectly leads to an increase in calcium ions stored in the sarcoplasmic reticulum. The increased calcium levels support a more forceful contraction of cardiac muscle, allowing the heart to work more efficiently.

Although used as a heart drug today, Withering used digitalis for a wide variety of ailments, including anasarca (generalized edema), epilepsy, hydrothorax (fluid in the pleural cavities), ovarian dropsy, and phthisis pulmonalis (probably tuberculosis). Sometimes Withering used digitalis as a treatment of last resort, "...whilst I was less expert in the management of the Digitalis, I seldom prescribed it, but when the failure of every other method compelled me to do it... if the properties of that plant had not been discovered, by far the greatest part of these patients would have died."

Not that digitalis is really a wonder drug. In fact, it is pretty toxic. According to Withering, "the Foxglove, when given in large and quickly-repeated doses, occasions sickness, vomiting, purging, giddiness, confused vision, objects appearing green or yellow; increased secretion of urine...slow pulse, even as slow as 35 in a minute, cold sweats, convulsions, syncope (unconsciousness), death."

The visual aberrations caused by digitalis include a tipping of the color scale toward yellow (xanthopsia), and halos around bright points of light. Such effects are displayed in some of the later works of Vincent van Gogh, his "yellow period." Halos around the stars and moon are evident in his famous painting "The Starry Night" and other works. It has been theorized that these effects are due to his use of foxglove to treat epilepsy. This idea was suggested by many self-portraits which included depictions of foxglove as well as two paintings of his doctor, which show him holding sprays of the flower. However, similar visual effects are caused by alkaloids in Artemisia absinthium, which is used to brew absinthe, a liqueur that Van Gogh was known to enjoy.

Digoxin was apparently the poison of choice for Charles Edmund Cullen, a nurse who may be the most prolific serial killer in American history, arrested in 2003 after a sixteen year murder spree. He specifically remembers killing at least 40 patients, but there is evidence to suggest that he may actually be responsible for hundreds of deaths.