Digitalis

For the medication sometimes called "Digitalis", see Digoxin.

Digitalis is a genus of about 20 species of herbaceous perennials, shrubs, and biennials that was traditionally placed in the figwort family Scrophulariaceae. Due to new genetic research, it has now been placed in the much enlarged family Plantaginaceae. The genus is native to Europe, western and central Asia, and northwestern Africa. The members of this genus are known in English as foxgloves. The scientific name means "finger-like" and refers to the ease with which a flower of Digitalis purpurea can be fitted over a human fingertip. The flowers are produced on a tall spike, are tubular, and vary in colour with species, from purple to pink, white, and yellow. The best-known species is the Common Foxglove, Digitalis purpurea. It is a biennial, often grown as an ornamental plant due to its showy flowers, that range in colour from purples through to whites, with variable marks and spotting. The first year of growth produces only the long, basal leaves. In the second year, the erect leafy stem 0.5-2.5 m tall develops. The larvae of the Foxglove Pug feed on the flowers of Digitalis purpurea. Other Lepidoptera species feed on the leaves including Lesser Yellow Underwing.

The term digitalis is also used for preparations containing cardiac glycosides, particularly digoxin, extracted from plants of this genus.

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Medicinal use

Medicines from foxgloves are called "Digitalin". The use of Digitalis purpurea extract containing cardiac glycosides for the treatment of heart conditions was first described by William Withering, in 1785, which is considered the beginning of modern therapeutics (Silverman)^[1][2] It is used to increase cardiac contractility (it is a positive inotrope) and as an antiarrhythmic agent to control the heart rate, particularly in the irregular (and often fast) atrial fibrillation. It is therefore often prescribed for patients in atrial fibrillation, especially if they have been diagnosed with heart failure.

A group of pharmacologically active compounds are extracted mostly from the leaves of the second year's growth, and in pure form are referred to by common chemical names such as digitoxin or digoxin, or by brand names such as Crystodigin and Lanoxin, respectively. The two drugs differ in that Digoxin has an additional hydroxyl group at the C-3 position on the B-ring (adjacent to the pentane). Both molecules include a lactone and a triple-repeating sugar called a glycoside.

Digitalis works by inhibiting sodium-potassium ATPase. This results in an increased intracellular concentration of sodium, which in turn increases intracellular calcium by passively decreasing the action of the sodium-calcium exchanger in the sarcolemma. The increased intracellular calcium gives a positive inotropic effect. It also has a vagal effect on the parasympathetic nervous system, and as such is used in reentrant cardiac arrhythmias and to slow the ventricular rate during atrial fibrillation. The dependence on the vagal effect means that digitalis is not effective when a patient has a high sympathetic nervous system drive, which is the case with acutely ill persons, and also during exercise.

Digitalis toxicity (Digitalis intoxication) results from an overdose of digitalis and causes anorexia, nausea, vomiting and diarrhea, as well as sometimes resulting in xanthopsia (jaundiced or yellow vision) and the appearance of blurred outlines (halos). Bradycardia also occurs. Because a frequent side effect of digitalis is reduction of appetite, some individuals have abused the drug as a weight loss aid.

Digitalis is a classic example of a drug derived from a plant formerly used by folklorists and herbalists: herbalists have largely abandoned its use because of its narrow therapeutic index and the difficulty of determining the amount of active drug in herbal preparations. Once the usefulness of digitalis in regulating pulse was understood, it was employed for a variety of purposes, including the treatment of epilepsy and other seizure disorders, now considered inappropriate.

Toxicity

Depending on the species, the digitalis plant may contain several deadly physiological and chemically related cardiac and steroidal glycosides. Thus, the digitalis has earned several more sinister monikers: Dead Man’s Bells, and Witches’ Gloves.

The entire plant is a poison (including the roots and seeds), although the leaves of the upper stem are particularly potent, with just a nibble being enough to potentially cause death. Early symptoms of ingestion include nausea, vomiting, anorexia, diarrhea, abdominal pain, wild hallucinations, delirium, and severe headache. Depending on the severity of the toxicosis the victim may later suffer irregular and slow pulse, tremors, various cerebral disturbances, especially of a visual nature (unusual color visions with objects appearing yellowish to green, and blue halos around lights), convulsions, and deadly disturbances of the heart. For a case description, see the paper by Lacassie.^[3]

There have been instances of people confusing digitalis with the harmless Symphytum (comphrey) plant (which is often brewed into a tea) with fatal consequences. Other fatal accidents involve children drinking the water in a vase containing digitalis plants. Drying does not reduce the toxicity of the plant. The plant is toxic to animals including all classes of livestock, as well as cats and dogs.

Digitalis poisoning can cause heart block and bradycardia (lowered heart rate) and tachycardia (increased heart rate). It is often quoted around the Internet that only bradycardia is associated with digitalis poisoning, but that is not true. It can cause either, depending on the dose and the condition of one's heart. It should however be noted, that electric cardioversion (to "shock" the heart) is generally not indicated in ventricular fibrillation in digitalis toxicity, as it can increase the dysrhythmia in digitalis toxicity. Also, the classic drug of choice (www.erc.edu) for VF (ventricular fibrillation) in emergency setting, amiodarone (cordarone(R)) can worsen the dysrhythmia caused by digitalis, therefore, the second choice drug Lidocaine (100mg) is to be used.

Use in molecular biology as digoxigenin

Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants Digitalis purpurea and Digitalis lanata. It is used as a molecular probe to detect DNA or RNA. It can easily be attached to nucleotides by chemical modifications. DIG molecules are often linked to uridine nucleotides; DIG labeled uridine (DIG-U) can then be incorporated into RNA probes via in vitro transcription. Once hybridisation occurs in situ, RNA probes with the incorporated DIG-U can be detected with anti-DIG antibodies that are conjugated to alkaline phosphatase. To reveal the hybridised transcripts, alkaline phosphatase can be reacted with a chromogen to produce a colour precipitate.

Appearances in fiction

• M*A*S*H: In an episode where Hot Lips shows a sense of humor while taking an inventory of medications with Hawkeye, Hawkeye asks, "Digitalis?" and Hot Lips replies, "No, I'm keeping a secret."

• X-Files: Digitalis was the sweet-tasting poison used in a series of murders by several genetically-identical children in the X-Files episode Eve (Season 1, Episode 10).^[4]

• Casino Royale: Digitalis was the poison that caused James Bond to nearly die from cardiac arrest in the 2006 movie Casino Royale. He was saved with an intravenous injection of lidocaine and a defibrillator jolt to get his heart pumping again.

• Psych: Digitalis was the poison used in the episode "From the Earth to the Starbucks" (Season 1, Episode 10).

• All My Children: Dixie, a character on the American soap opera All My Children, suffered from a heart condition which required her to take digitalis.

• Silas Marner: Foxglove appears briefly in the George Elliot novel when Silas uses the drug to help a sick village woman with a heart condition.

• The Yellow Admiral: Digitalis is prescribed by Stephen Maturin for the ailing vice-admiral Lord Stranraer. The admiral's physician is warned to avoid letting the patient know the name of the drug he is being dosed with and to prevent access to it. After the patient leaves Dr. Maturin's care, it is later reported that Lord Stranraer's condition has deteriorated greatly due to him dosing himself.

• The Sandman (Vertigo): The character of Donna Cavanagh changed her name to Foxglove after a tramatic break-up. She was passing a flower shop and noticed a set of flowers. Asking what they were, she was told that they were foxgloves and they were meant to have healing qualities. Donna found it fitting and choose it as her new name.

• The Lust Lizard of Melancholy Cove: Joseph Leander kills his wife Bess by giving her foxglove tea in this Christopher Moore novel.

• VALIS: In the 1981 psychedelic sci-fi novel, VALIS, by Philip K. Dick, the main character, Horselover Fat tries to kill himself in 1976 by slitting his wrist, taking 49 tablets of high grade digitalis, and sitting in a closed garage with his car motor running. His second failed suicide attempt.

• House MD: In episode twelve of the first season of the medical drama House MD, pitcher Hank Wiggin downs a bottle of Digitalis as a suicide attempt in order to convince his wife to forestall getting an abortion. His wife was considering the operation in order to make herself a viable kidney doner for Hank, whose kidneys were failing as a symptom of cadmium poisoning.

• Precious Bane: In this 1924 novel by Mary Webb, some digitalis in tea helps further plans of Gideon Sarn.

Gallery

References

1. ^ . In contemporary medicine, a purer form of digitalis (usually digoxin) is obtained from Digitalis lanata.
2. ^ Digoxin comes from Digitalis lanata. Hollman A. BMJ 1996;312:912. online version accessed 18 Oct 2006 [1]
3. ^ A non-fatal case of intoxication with foxglove, documented by means of liquid chromatography-electrospray-mass spectrometry. Lacassie E et al, J Forensic Sci. 2000 Sep;45(5):1154-8. Abstract accessed online 19 Sep 2006. [2]
4. ^ http://redwolf.com.au/xfiles/season01/1x10.html