Clinical Use of Digitalis: A State of the Art Review

Thomas F. Whayne Jr

Disclosures

Am J Cardiovasc Drugs. 2018;18(6):427-440. 

In This Article

History of Digitalis

So-called herbal diuretics have a long history, being used as early as 2000 years ago, with folk medicine contributing to William Withering's use of the foxglove in the eighteenth century.[3] Apparently, Greek physicians were unaware of herbs with digitalis glycoside activity.[4] However, the Romans were reported to have used the foxglove as a medication for heart failure.[5] In the middle ages, topically applied plant extracts (inunction) with physiological activity were well-known in folk medicine, with effects that can now be recognized as an overdose of digitalis glycosides.[4]

William Withering

William Withering's eighteenth century contribution to modern cardiovascular medicine is well-known. He was apparently unaware of many of the effects of foxglove on the heart, but his classic treatise published in 1785 described his successful treatment of many patients with congestive heart failure (CHF) and several examples of digitalis toxicity.[2] His reported results in 163 patients with so-called hydropsy (water retention) treated with foxglove (Digitalis purpurea) identified responders as having CHF as compared with nonresponders.[6] Withering was the first physician to compare the condition of his patients before and after treatment and to define the individual clinical characteristics of those who responded to treatment.[6] He was a member of the prestigious Lunar Society, was well-established as a skilled physician, and was also known as a botanist,[7] the latter of which was certainly of significance to his contribution. Withering was apparently a compulsive observer who recorded detailed descriptions of his observations, which is of special note when bleeding of the patient was still the major treatment for CHF.[7] Withering's publication of An Account of the Foxglove and Some of its Medical Uses: With Practical Remarks on Dropsy and Other Disease can be considered a major turning point in the history of medicine as a profession.[7] Lessons from his reported studies remain relevant in current pharmacology and epidemiology and can be summarized as follows.[8]

  1. Withering found that failure to prepare digitalis from the foxglove in a specified consistent manner resulted in inconsistent clinical effects. Unfortunately, in the current era, many medications prepared from plants still involve inconsistent methodology with subsequent quality problems.

  2. Withering noted different patient responses to digitalis, although he did not understand basic pharmacological effects such as variations in receptor sensitivity and drug disposition.

  3. However, he was aware of the dose–response characteristics of digitalis through clinical observation, although he did not have biomarkers available.

  4. Withering documented many adverse effects from digitalis, consideration of which can be seen as the beginning of clinical toxicology and benefit/risk profiles.[8]

Vincent van Gogh

The great Dutch postimpressionist painter, Vincent Van Gogh, who died in 1890,[9] is relevant to the history of digitalis.[10] His medical record was bizarre and apparently included automutilation, depression, insanity, and, ultimately, suicide. Relevant to this review, his paintings during his later years of life were characterized by halos and the color yellow. While art critics attribute these characteristics to conditions such as chronic solar injury, cataracts, and glaucoma, Van Gogh may have experienced the side effects of digitalis intoxication as manifested by xanthopsia and coronas.[10] The basis of this theory is that two of Van Gogh's paintings are portraits of his physician holding a foxglove plant.[10] Xanthopsia is an overriding yellow bias in vision and is classically associated with digitalis toxicity, although it has also been associated with some other drugs and even snake venom.[9] The possibility of digitalis toxicity in the case of Vincent Van Gogh, especially with the dominance of yellow hues in his paintings, is a prime consideration but remains speculative and not strictly proven, with other reasons also possible.[9] Although excess consumption of absinthe is also a major consideration for the yellow in Van Gogh's works, since this liquor is associated with xanthopsia, digitalis intoxication can be considered more likely as Van Gogh had epilepsy, and common practice at the time was to treat epilepsy with digitalis.[11] In any event, this all makes for interesting speculation regarding the great painter.

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