Digitalis

Digitalis (/ˌdɪdʒɪˈteɪlɪs/[1] or /ˌdɪdʒɪˈtælɪs/[2]) is a genus of about 20 species

Foxglove
of herbaceous perennials, shrubs, and biennials commonly called foxgloves.

This genus was traditionally placed in the figwort family Scrophulariaceae,

but recent phylogenetic research has placed it in the much enlarged family
Plantaginaceae.[3] This genus is native to western and southwestern Europe,[4]
western and central Asia and northwestern Africa. 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.
This biennial plant is often grown as an ornamental plant due to its vivid
flowers which range in colour from various purple tints through pink, and
purely white. The flowers can also possess various marks and spottings. The
first year of growth produces only the stem with its long, basal leaves. During
the second year of the plant's life, a long, leafy stem from 50 to 255
centimetres tall grows atop the roots of healthy plants.
Digitalis purpurea (Common foxglove)
Other garden-worthy species include D. ferruginea, D. grandiflora, D. lutea
Scientific classification
and D. parviflora.[5]
Kingdom: Plantae
Larvae of the foxglove pug, a moth, consume the flowers of the common
Clade: Tracheophytes
foxglove for food. Other species of Lepidoptera eat the leaves, including the
lesser yellow underwing. Clade: Angiosperms
Clade: Eudicots
The term digitalis is also used for drug preparations that contain cardiac
glycosides, particularly one called digoxin, extracted from various plants of Clade: Asterids
this genus.
Order: Lamiales
Family: Plantaginaceae
Tribe: Digitalideae
Contents
Genus: Digitalis
Etymology
L.
Habitat
Medicinal uses Species
Cardiac
Variations Over 20 species, including:
Mechanism of action Digitalis canariensis
Digitalis cariensis
Toxicity
Digitalis ciliata
Digoxigenin
Digitalis davisiana
References
Digitalis dubia
External links
Digitalis ferruginea
Etymology Digitalis × fulva
Digitalis grandiflora
The name "foxglove" was first recorded in the year 1542 by Leonhard Fuchs, Digitalis isabelliana
whose family name, Fuchs, is the German word for "fox" (the plant genus Digitalis laevigata
Fuchsia is also named for him). The genus digitalis is from the Latin digitus Digitalis lanata
(finger), perhaps referencing the shape of the flowers, which accommodate a Digitalis leucophaea
finger when fully formed.[6] Digitalis lutea
Digitalis mariana
Thus the name is recorded in Old English as foxes glofe/glofa or fox's glove.[7]
Digitalis micrantha
Over time, folk myths obscured the literal origins of the name, insinuating that
Digitalis obscura
foxes wore the flowers on their paws to silence their movements as they
Digitalis parviflora
stealthily hunted their prey. The woody hillsides where the foxes made their
Digitalis purpurea
dens were often covered with the toxic flowers. Some of the more menacing
Digitalis sceptrum
names, such as "witch's glove," reference the toxicity of the plant.[8]
Digitalis thapsi
Henry Fox Talbot (1847) proposed folks' glove, where folk means fairy.[7] Digitalis trojana
Similarly, R. C. A. Prior (1863) suggested an etymology of foxes-glew, Digitalis viridiflora
meaning 'fairy music'.[7] However, neither of these suggestions account for
the Old English form foxes glofa.[9]

Habitat
Digitalis species thrive in acidic soils, in partial sunlight to deep shade, in a range of
habitats, including open woods, woodland clearings, moorland and heath margins, sea-
cliffs, rocky mountain slopes and hedge banks.[4][10] It is commonly found on sites where
the ground has been disturbed, such as recently cleared woodland, or where the vegetation
has been burnt.[11]

Medicinal uses

Cardiac Digitalis lutea

A group of medicines extracted from foxglove plants are called digitalin. The use of D.
purpurea extract containing cardiac glycosides for the treatment of heart
conditions was first described in the English-speaking medical literature by
William Withering, in 1785,[12][13][14] which is considered the beginning of
modern therapeutics.[15][16] 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. Digitalis is hence
often prescribed for patients in atrial fibrillation, especially if they have been
diagnosed with congestive heart failure. Digoxin was approved for heart failure
in 1998 under current regulations by the Food and Drug Administration on the
basis of prospective, randomized study and clinical trials. It was also approved Pink common foxglove with bee
for the control of ventricular response rate for patients with atrial fibrillation.
American College of Cardiology/American Heart Association guidelines
recommend digoxin for symptomatic chronic heart failure for patients with reduced systolic function, preservation of systolic
function, and/or rate control for atrial fibrillation with a rapid ventricular response. Heart Failure Society of America guidelines
for heart failure provide similar recommendations. Despite its relatively recent approval by the Food and Drug Administration
and the guideline recommendations, the therapeutic use of digoxin is declining
in patients with heart failure—likely the result of several factors. Safety concerns
regarding a proposed link between digoxin therapy and increased mortality in
women may be contributing to the decline in therapeutic use of digoxin.

Variations
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.

Mechanism of action
Digitalis works by inhibiting sodium-potassium ATPase. This results in an
increased intracellular concentration of sodium ions and thus a decreased
concentration gradient across the cell membrane. This increase in intracellular
Hendrik Goltzius, A Foxglove in
sodium causes the Na/CA exchanger to reverse potential, i.e., transition from
Bloom, 1592, National Gallery of Art,
pumping sodium into the cell in exchange for pumping calcium out of the cell, to
NGA 94900
pumping sodium out of the cell in exchange for pumping calcium into the cell.
This leads to an increase in cytoplasmic calcium concentration, which improves
cardiac contractility. Under normal physiological conditions, the cytoplasmic
calcium used in cardiac contractions originates from the sarcoplasmic reticulum,
an intracellular organelle that specializes in the storage of calcium. Human
newborns, some animals, and patients with chronic heart failure lack well
developed and fully functioning sarcoplasmic reticula and must rely on the
Na/Ca exchanger to provide all or a majority of the cytoplasmic calcium
required for cardiac contraction. For this to occur, cytoplasmic sodium must
exceed its typical concentration to favor a reversal in potential, which naturally
occurs in human newborns and some animals primarily through an elevated
heart rate; in patients with chronic heart failure it occurs through the
administration of digitalis. As a result of increased contractility, stroke volume is
increased. Ultimately, digitalis increases cardiac output (Cardiac Output=Stroke
Volume x Heart Rate). This is the mechanism that makes this drug a popular
treatment for congestive heart failure, which is characterized by low cardiac
output. Digitalis also has a vagal effect on the parasympathetic nervous system,
and as such is used in re-entrant cardiac arrhythmias and to slow the ventricular
rate during atrial fibrillation. The dependence on the vagal effect means 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.
A patch of Digitalis purpurea and
Digitalis lutea in Seattle, WA.
Toxicity
Digitalis toxicity (also known as digitalis intoxication and digitalism) results
from an overdose of digitalis and causes nausea, vomiting and diarrhea, as well
as sometimes resulting in xanthopsia (jaundiced or yellow vision) and the
appearance of blurred outlines (halos), drooling, abnormal heart rate, cardiac
arrhythmias, weakness, collapse, dilated pupils, tremors, seizures, and even
death. Bradycardia also occurs. Because a frequent side effect of digitalis is
reduction of appetite, some individuals have used the drug as a weight-loss aid.

Digitalis is an example of a drug derived from a plant that was 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 the
human pulse was understood, it was employed for a variety of purposes,
including the treatment of epilepsy and other seizure disorders, which are now
Digitalis purpurea -- light purple
considered to be inappropriate treatments.

Depending on the species, the digitalis plant may contain several deadly
physiological and chemically related cardiac and steroidal glycosides. Thus, the
digitalis plants have earned several, more sinister, names: dead man’s bells and
witch's gloves.

The entire plant is toxic (including the roots and seeds). Mortality is rare, but
case reports do exist. Most plant exposures occur in children younger than six
years and are usually unintentional and without associated significant toxicity.
More serious toxicity occurs with intentional ingestions by adolescents and
adults.[17] Early symptoms of ingestion include nausea, vomiting, 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 colour visions (see xanthopsia) with objects appearing yellowish to
green, and blue halos around lights), convulsions, and deadly disturbances of the Digitalis purpurea drawings by Franz
heart. For a case description, see the paper by Lacassie.[18] Vincent van Gogh's Köhler
"Yellow Period" may have been influenced by digitalis therapy which, at the
time, was thought to control seizures. As noted above, other oculotoxic effects of
digitalis include generalized blurry vision, as well as seeing a "halo" around each point of light.[19]

In some instances, people have confused digitalis with the relatively harmless comfrey (Symphytum) 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.[20] Drying does not reduce the toxicity of the plant. The plant is toxic to animals, including all classes of livestock and
poultry, as well as felines and canines.

Digitalis poisoning can cause heart block and either bradycardia (decreased heart rate) or tachycardia (increased heart rate),
depending on the dose and the condition of one's heart. Notably, the electric cardioversion (to "shock" the heart) is generally not
indicated in ventricular fibrillation in digitalis toxicity, as it can increase the dysrhythmia.[21][22] Also, the classic drug of choice
for ventricular fibrillation in emergency setting,[23] amiodarone, can worsen the dysrhythmia caused by digitalis, therefore, the
second-choice drug lidocaine is more commonly used.[24]

Digoxigenin
Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants D. purpurea and D. 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-labelled 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 coloured precipitate.

References
1. OED: "Digitalis"
2. Digitalis (http://dictionary.reference.com/browse/digitalis) at Dictionary.com]
3. Olmstead, R. G.; dePamphilis, C. W.; Wolfe, A. D.; Young, N. D.; Elisons, W. J. & Reeves P. A. (2001).
"Disintegration of the Scrophulariaceae" (http://www.amjbot.org/cgi/content/full/88/2/348). American Journal of
Botany. American Journal of Botany, Vol. 88, No. 2. 88 (2): 348–361. doi:10.2307/2657024 (https://doi.org/10.230
7%2F2657024). JSTOR 2657024 (https://www.jstor.org/stable/2657024). PMID 11222255 (https://www.ncbi.nlm.
nih.gov/pubmed/11222255).
4. Anon. "Foxglove (Digitalis purpurea)" (https://web.archive.org/web/20100613180131/http://www.arkive.org/foxglo
ve/digitalis-purpurea/range-and-habitat.html). Arkive: images of life on Earth. Wildscreen. Archived from the
original (http://www.arkive.org/foxglove/digitalis-purpurea/range-and-habitat.html) on 13 June 2010. Retrieved
6 May 2010.
5. Brickell, Christopher, ed. (2008). The Royal Horticultural Society A-Z Encyclopedia of Garden Plants. United
Kingdom: Dorling Kindersley. p. 377. ISBN 9781405332965.
6. Hollman, A (September 1985). "Plants and cardiac glycosides" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4
81893). Br. Heart J. 54 (3): 258–261. doi:10.1136/hrt.54.3.258 (https://doi.org/10.1136%2Fhrt.54.3.258).
PMC 481893 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC481893). PMID 4041297 (https://www.ncbi.nlm.nih.
gov/pubmed/4041297).
7. Liberman, Anatoly (10 November 2010). "Etymologists at War with a Flower: Foxglove | OUPblog" (https://web.ar
chive.org/web/20130508161659/http://blog.oup.com/2010/11/foxglove/). Archived from the original (http://blog.ou
p.com/2010/11/foxglove/) on 8 May 2013. Retrieved 10 August 2015.
8. "Foxglove" (https://www.uaex.edu/yard-garden/resource-library/plant-week/foxglove.aspx). Foxglove. Retrieved
17 April 2018.
9. Liberman, Anatoly (10 November 2010). "Etymologists at War with a Flower: Foxglove | OUPblog" (https://web.ar
chive.org/web/20130508161659/http://blog.oup.com/2010/11/foxglove/). Archived from the original (http://blog.ou
p.com/2010/11/foxglove/) on 8 May 2013. Retrieved 10 August 2015.

Liberman writes: "In sum, foxglove means foxglove, and this disturbing fact has to be accepted."
10. Anon. "Foxglove: Digitalis purpurea (Scrophulariaceae)" (http://aggie-horticulture.tamu.edu/wildseed/27/27.4.htm
l). Wildflowers in Bloom. Wildseed farms. Retrieved 7 May 2010.
11. Klein, Carol (18 May 2002). "How to grow: Foxgloves" (https://www.telegraph.co.uk/gardening/howtogrow/33005
21/How-to-grow-Foxgloves.html). The Telegraph. London, UK: Telegraph Media Group Limited. Retrieved 6 May
2010.
12. William Withering, An Account of the Foxglove and some of its Medical Uses (https://books.google.com/books?id
=VgIta49rzT4C&pg=PR3#v=onepage&q&f=false) (Birmingham, England: M. Swinney, 1785).
13. Goldthorp WO (2009). "Medical Classics: An Account of the Foxglove and Some of its Medicinal Uses by William
Withering, published 1785". Br Med J. 338: b2189. doi:10.1136/bmj.b2189 (https://doi.org/10.1136%2Fbmj.b218
9).
14. Simpson, Beryl Brintnall; Ogorzaly, Molly Coner (2001). Economic Botany (3rd ed.). Boston: Mc Graw Hill. p. 529.
ISBN 9780072909388.
15. In contemporary medicine, a purer form of digitalis (usually digoxin) is obtained from D. lanata.
16. Digoxin comes from Digitalis lanata. Hollman A. BMJ 1996;312:912. online version accessed 18 October 2006 [1]
(http://bmj.bmjjournals.com/cgi/content/full/312/7035/912)
17. "Cardiac Glycoside Plant Poisoning: Medscape reference" (http://emedicine.medscape.com/article/816781-overvi
ew#a0199). Retrieved 3 July 2012.
18. 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 September
2006. [2] (https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uid
s=11005196&query_hl=13&itool=pubmed_DocSum)
19. Goldfrank LW (2006). Goldfrank's Toxicologic Emergencies (8th ed.). New York: McGraw-Hill.
20. Anon. "Notes on poisoning:Digitalis purpura" (https://web.archive.org/web/20111013203513/http://www.cbif.gc.c
a/pls/pp/ppack.info?p_psn=57&p_type=all&p_sci=sci). Canadian poisonous plants information system. Canadian
Biodiversity Information Facility. Archived from the original (http://www.cbif.gc.ca/pls/pp/ppack.info?p_psn=57&p_
type=all&p_sci=sci) on 13 October 2011. Retrieved 9 March 2013.
21. Abou-Donia, Mohamed (2015). Mammalian Toxicology. John Wiley & Sons. p. 631. ISBN 9781118683316.
22. Robert Alan Lewis Lewis' Dictionary of Toxicology - 1998 Page 387 1566702232 See also digitalis. digitalis
poisoning. digitalism; acute or cumulative chronic poisoning by digitalis. Symptoms may include gastrointestinal
disturbances and pain, severe headache, nausea, vomiting, diarrhea, irregular pulse, and yellow vision ...
23. "European Resuscitation Council" (http://www.erc.edu).
24. Lee Lopez, Orchid (2011). Back to Basics: Critical Care Transport Certification Review. Xlibris Corporation.
p. 290. ISBN 9781456862749.

External links
Flora Europaea: Digitalis species list (http://rbg-web2.rbge.org.uk/cgi-bin/nph-readbtree.pl/feout?FAMILY_XREF=
&GENUS_XREF=Digitalis&SPECIES_XREF=&TAXON_NAME_XREF=&RANK=species)
Molecule of the Month - Digitalis (http://www.bris.ac.uk/Depts/Chemistry/MOTM/digitalis/digtalis.htm)
eMedicine link (http://www.emedicine.com/PED/topic590.htm)
"Foxglove" (https://en.wikisource.org/wiki/Collier%27s_New_Encyclopedia_(1921)/Foxglove). Collier's New
Encyclopedia. 1921.

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