Editing Digitalis

{{Short description|Genus of flowering plants in the family Plantaginaceae}}
{{Redirect|Foxglove}}
{{About||the pharmaceutical|Digoxin|the foxglove-tree, which has similar-looking blooms|Paulownia tomentosa}}
{{Use dmy dates|date=December 2020}}
{{Automatic taxobox
|image = Digitalis purpurea2.jpg
|image_caption = ''[[Digitalis purpurea]]'' (Common foxglove)
|taxon = Digitalis
|authority = [[Tourn.]] ex [[Carl Linnaeus|L.]]<ref name=PoWO>{{cite web |title=''Digitalis'' Tourn. ex L. |date=2017 |work=[[Plants of the World Online]] |publisher=[[Royal Botanic Gardens, Kew]] |url=http://powo.science.kew.org/taxon/30112738-2 |access-date=22 November 2020}}</ref>
|subdivision_ranks = Species
|subdivision = Over 20 species, see text:
|type_species = ''[[Digitalis purpurea]]'' [[L.]]<ref name = "Tropicos">Missouri Botanical Garden. (n.d.-p). ''Digitalis'' L. Tropicos. Retrieved February 19, 2025, from https://www.tropicos.org/name/40030988</ref>
}}
[[Image:Digitalis lutea 100705.jpg|thumb|right|upright|''[[Digitalis lutea]]'']]
[[File:Common-foxglove-285364 960 720.jpg|thumb|middle|Pink common foxglove with bee]]
[[File:Picture of a digitalis.jpg|thumb|''Digitalis'' blossoms and immature flowers]]

'''''Digitalis''''' ({{IPAc-en|ˌ|d|ɪ|dʒ|ᵻ|ˈ|t|eɪ|l|ᵻ|s}}<ref>''[[Oxford English Dictionary]]:'' "Digitalis"</ref> or {{IPAc-en|ˌ|d|ɪ|dʒ|ᵻ|ˈ|t|æ|l|ᵻ|s}}<ref>{{cite web |url=http://dictionary.reference.com/browse/digitalis |title=Digitalis |author=<!--Not stated--> |website=Dictionary.com }}</ref>) is a genus of about 20 species of herbaceous perennial plants, [[shrub]]s, and [[Biennial plant|biennials]], commonly called '''foxgloves'''.

''Digitalis'' is native to Europe, Western Asia, and northwestern Africa. The flowers are tubular in shape, produced on a tall spike, and vary in colour with species, from purple to pink, white, and yellow. The name derives from the Latin word for "finger".<ref>{{Cite web |title=Definition of DIGITALIS |url=https://www.merriam-webster.com/dictionary/digitalis |access-date=2024-05-03 |website=www.merriam-webster.com |language=en}}</ref> The genus was traditionally placed in the figwort family, [[Scrophulariaceae]], but [[phylogenetic]] research led taxonomists to move it to the [[Veronicaceae]] in 2001.<ref name="olmstead">{{Cite journal|last1=Olmstead |first1=R. G. |last2=de Pamphilis |first2=C. W. |last3=Wolfe |first3=A. D. |last4=Young |first4=N. D. |last5=Elisons |first5=W. J. |last6=Reeves |first6=P. A. |title=Disintegration of the Scrophulariaceae |journal=American Journal of Botany |volume=88 |issue=2 | pages = 348–361| year=2001 |url=https://www.researchgate.net/publication/280820806 |doi=10.2307/2657024 |pmid=11222255 |jstor=2657024 |access-date=28 November 2020|doi-access=free }}</ref> More recent phylogenetic work has placed it in the much enlarged family [[Plantaginaceae]].

The best-known species is the common foxglove, ''[[Digitalis purpurea]]''. This biennial 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. Other garden-worthy species include ''D. ferruginea'', ''D. grandiflora'', ''D. lutea'', and ''D. parviflora''.<ref name=AZEGP>{{cite book |editor-last= Brickell |editor-first=Christopher |title=The Royal Horticultural Society A-Z Encyclopedia of Garden Plants |year=2008 |page=377 |publisher=Dorling Kindersley |isbn=9781405332965}}</ref>

The term ''digitalis'' is also used for drug preparations that contain [[cardiac glycoside]]s, particularly one called [[digoxin]], extracted from various plants of this genus. Foxglove has medicinal uses but is also very toxic to humans and other mammals, such that consumption can cause serious illness or death.<ref>{{Cite web |last=Trust |first=Woodland |date=2020-01-07 |title=Foxglove and other poisonous plants |url=https://www.woodlandtrust.org.uk/blog/2020/07/uk-poisonous-plants/ |access-date=2024-06-01 |website=Woodland Trust |language=en-GB}}</ref>

==Etymology==
[[File:Hendrik Goltzius, A Foxglove in Bloom, 1592, NGA 94900.jpg|alt=Brown pen and ink of a foxglove in bloom|thumb|Hendrik Goltzius, A Foxglove in Bloom, 1592, [[National Gallery of Art]], NGA 94900]]
The [[generic epithet]] ''Digitalis'' is from the Latin ''digitus'' (finger).<ref>{{cite journal |last1=Hollman |first1=A |date=September 1985 |title=Plants and cardiac glycosides |journal=British Heart Journal |volume= 54 |issue=3 |pages=258–261 |pmc=481893 |doi=10.1136/hrt.54.3.258 |pmid=4041297}}</ref> [[Leonhart Fuchs]] first invented the name for this plant in his 1542 book ''De historia stirpium commentarii insignes'' (''Notable comments on the history of plants''), based upon the German [[vernacular name]] ''Fingerhut'',<ref>{{cite book |last=Fuchs |first=Leonhart |author-link=Leonhart Fuchs |date=1542 |title=De historia stirpium commentarii insignes |location=Basel |publisher=In officina Isingriniana |pages=892–893 |language=la |quote=''Apellauimus autem Digitalem, alludentes ad germanicam nomenclaturam...''}}</ref><ref name=Klingaman2002>{{Cite web |url=https://www.uaex.edu/yard-garden/resource-library/plant-week/foxglove.aspx |title=Plant of the Week: Foxglove |last=Klingaman |first=Gerald |date=17 May 2002 |website=University of Arkansas System Division of Agriculture |language=en |access-date=2018-04-17 |archive-date=22 April 2020 |archive-url=https://web.archive.org/web/20200422191357/https://www.uaex.edu/yard-garden/resource-library/plant-week/foxglove.aspx |url-status=dead }}</ref> which translates literally as 'finger hat', but actually means 'thimble'.

The name is recorded in [[Old English]] as 'foxes glofe/glofa' or 'fox's glove'.<ref name="Liberman-2010">{{Cite web |title = Etymologists at War with a Flower: Foxglove |website=OUPblog |url = http://blog.oup.com/2010/11/foxglove/ |access-date=2015-08-10 |date=2010-11-10 |last=Liberman |author-link = Anatoly Liberman |first=Anatoly |archive-url=https://web.archive.org/web/20130508161659/http://blog.oup.com/2010/11/foxglove/ |archive-date=2013-05-08 |quote="In sum, foxglove means foxglove, and this disturbing fact has to be accepted."}}</ref> Over time, folk myths obscured the literal origins of the name, insinuating that foxes wore the flowers on their paws to silence their movements as they stealthily hunted their prey. The woody hillsides where the foxes made their dens were often covered with the toxic flowers. Some of the more menacing names, such as "witch's glove", reference the toxicity of the plant.<ref name=Klingaman2002/>

[[Henry Fox Talbot]] (1847) proposed 'folks' glove', where 'folk' means fairy. Similarly, R. C. A. Prior (1863) suggested an etymology of 'foxes-glew', meaning 'fairy music'. However, neither of these suggestions account for the Old English form ''foxes glofa''.<ref name="Liberman-2010" />

==Taxonomy==
It was published by [[Carl Linnaeus]] in 1753.<ref name = "Linnaeus, 1753">Linné,  Carl von, & Salvius,  Lars. (1753). Caroli Linnaei ... Species plantarum :exhibentes plantas rite cognitas, ad genera relatas, cum differentiis specificis, nominibus trivialibus, synonymis selectis, locis natalibus, secundum systema sexuale digestas... (Vol. 2, p. 621). Impensis Laurentii Salvii. https://www.biodiversitylibrary.org/page/358642</ref><ref name = "Tropicos" /> The lectotype species ''[[Digitalis purpurea]]'' [[L.]] was designated in 1930.<ref name = "Tropicos" />
===Species===
The ''[[Flora Europaea]]'' originally recognised a number of species now seen as synonyms of ''Digitalis purpurea'', or others: ''D. dubia'', ''D. leucophaea'', ''D. micrantha'' and ''D. trojana''.<ref>{{cite web| url = http://rbg-web2.rbge.org.uk/cgi-bin/nph-readbtree.pl/feout?FAMILY_XREF=&GENUS_XREF=Digitalis&SPECIES_XREF=&TAXON_NAME_XREF=&RANK=species| title = ''Flora Europaea'': ''Digitalis'' species list}}</ref> As of 2017, ''[[Plants of the World Online]]'' recognises the following 27 species (and a number of hybrids):<ref name=PoWO/>
*''[[Digitalis atlantica]]'' <small>Pomel</small>
*''[[Digitalis canariensis]]'' <small>[[Carl Linnaeus|L.]]</small>
*''[[Digitalis cariensis]]'' <small>[[Boiss.]] ex [[Jaub.]] & [[Édouard Spach|Spach]]</small>
*''[[Digitalis cedretorum]]'' <small>([[Emb.]]) [[René Maire|Maire]]</small>
*''[[Digitalis chalcantha]]'' <small>([[Svent.]] & O'Shan.) Albach, Bräuchler & Heubl</small>
*''[[Digitalis ciliata]]'' <small>[[Trautv.]]</small>
*''[[Digitalis davisiana]]'' <small>[[Vernon Hilton Heywood|Heywood]]</small>
*''[[Digitalis ferruginea]]'' <small>L.</small>
*''Digitalis fuscescens'' <small>[[Waldst.]] & Kit.</small>
*''[[Digitalis grandiflora]]'' <small>[[Mill.]]</small>
*''Digitalis ikarica'' <small>([[P.H.Davis]]) Strid</small>
*''[[Digitalis isabelliana]]'' <small>(Webb) Linding.</small>
*''[[Digitalis laevigata]]'' <small>Waldst. & Kit.</small>
*''[[Digitalis lamarckii]]'' <small>Ivanina</small>
*''[[Digitalis lanata]]'' <small>[[Ehrh.]]</small>
*''[[Digitalis lutea]]'' <small>L.</small>
*''[[Digitalis mariana]]'' <small>Boiss.</small>
*''[[Digitalis minor]]'' <small>L.</small>
*''[[Digitalis nervosa]]'' <small>[[Steud.]] & [[Hochst.]] ex [[Benth.]]</small>
*''[[Digitalis obscura]]'' <small>L.</small>
*''[[Digitalis parviflora]]'' <small>[[Jacq.]]</small>
*''[[Digitalis purpurea]]'' <small>L.</small>
*''[[Digitalis sceptrum]]'' <small>[[L.f.]]</small>
*''Digitalis subalpina'' <small>[[Braun-Blanq.]]</small>
*''[[Digitalis thapsi]]'' <small>L.</small>
*''[[Digitalis transiens]]'' <small>Maire</small>
*''[[Digitalis viridiflora]]'' <small>[[Lindl.]]</small>

===Hybrids===
*''[[Digitalis × coutinhoi]]'' <small>[[Samp.]]</small>
*''[[Digitalis × fulva]]'' <small>Lindl.</small>
*''Digitalis × macedonica'' <small>Heywood</small>
*''Digitalis × media'' <small>Roth</small>
*''Digitalis × pelia'' <small>Zerbst & Bocquet</small>
*''Digitalis × purpurascens'' <small>Roth</small>
*''Digitalis'' × ''sibirica'' <small>(Lindley) Werner</small> had been considered a valid species since it was first described by the English botanist and gardener [[John Lindley]] in 1821,<ref name=Lindley1821>{{cite book |last=Lindley |first=John |author-link=John Lindley |date=1821 |title=Digitalium monographia: sistens historiam botanicam generis, tabulis omnium specierum hactenus cognitarum illustratam ut plurimum confectis ad icones |url=https://www.biodiversitylibrary.org/page/58374153 |location=London |publisher=Arthur Taylor for J.H. Bohte |pages=1–27 |language=la |doi=10.5962/bhl.title.160067}}</ref> but it was considered a hybrid of ''D. grandiflora'' and ''D. laevigata'' by the German botanist {{ill|Klaus Werner|de|Klaus Werner (Botaniker)}} in 1960.<ref name=Eker2016>{{cite journal |last1=Eker |first1=İsmail |last2=Yücesan |first2=Buhara |last3=Sameeullah |first3=Muhammad |last4=Welß |first4=Walter |last5=Müller-Uri |first5=Frieder |last6=Gürel |first6=Ekrem |last7=Kreis |first7=Wolfgang |date=January 2016 |title=Phylogeny of Anatolian (Turkey) species in the ''Digitalis'' sect. ''Globiflorae'' (Plantaginaceae) |url=http://bap.ibu.edu.tr/Yurutucu/Dosyalar/E95042.pdf |archive-url=https://web.archive.org/web/20211202234658/http://bap.ibu.edu.tr/Yurutucu/Dosyalar/E95042.pdf |archive-date=2021-12-02 |url-status=live |journal=Phytotaxa |volume=244 |issue=3 |pages=263 |doi=10.11646/phytotaxa.244.3.3 |bibcode=2016Phytx.244..263E |s2cid=87777389 |issn=1179-3163 |access-date=25 November 2020}}</ref>

===Systematics===
The first full [[monograph]] regarding this genus was written by [[John Lindley|Lindley]] in 1821. He included two sections, a section ''[[Isoplexis]]'' including two species, and the main section ''Digitalis'' with three subsections, including 2Y species, a number of which are now seen as [[Synonym (taxonomy)|synonyms]] or hybrids.<ref name=Lindley1821/>

In the last full monograph of the genus in 1965, Werner classified the 19 recognised species in five [[Section (taxonomy)|sections]] (four species from [[Macaronesia]] were separated in the genus ''Isoplexis'' at the time):<ref>{{cite journal |last1=Werner |first1=Klaus |date=1965 |title=Taxonomie und Phylogenie der Gattungen ''Isoplexis'' (Lindl.) Benth. und ''Digitalis'' L. |journal=Feddes Repertorium |volume=70 |issue=1–3 |pages=109–135 |doi=10.1002/fedr.19650700106 |language=de}}</ref><ref name=Kreis2017>{{cite journal |last1=Kreis |first1=Wolfgang |date=2017 |title=The Foxgloves (''Digitalis'') Revisited |journal=Planta Medica |volume=83 |issue=12–13 |pages=962–976 |doi=10.1055/s-0043-111240|pmid=28561136 |doi-access=free |bibcode=2017PlMed..83..962K }}</ref><ref name=Wichtl2001>{{cite journal |last1=Wichtl |first1=Max |date=2001 |title=''Digitalis'' L. -Fingerhut (Scrophulariaceae) - eine wichtige Arzneipflanzengattung |url=https://archive.org/details/stapfia-75-089-100 |journal=Stapfia |volume=75 |issue=164 |pages=89–100 |language=de |access-date=25 November 2020}}</ref>
*In the section ''Digitalis'', along with the [[type species]] [[Digitalis purpurea|''D. purpurea'']], four other species (as recognised as the time) were placed: [[Digitalis thapsi|''D. thapsi'']], [[Digitalis purpurea#Subspecies and hybrids|''D. dubia'']], [[Digitalis mariana|''D. heywoodii'']] and [[Digitalis mariana|''D. mariana'']].
*The [[monotypic]] section ''Frutescentes'' contained only [[Digitalis obscura|''D. obscura'']].
*The section ''Grandiflorae'', which was also called section ''Macranthae'' by [[Vernon Hilton Heywood]]. It included, along with the [[type species]] ''D. grandiflora'', also [[Digitalis atlantica|''D. atlantica'']], [[Digitalis ciliata|''D. ciliata'']] and [[Digitalis davisiana|''D. davisiana'']].
*''Globiflorae'' included five species: [[Digitalis laevigata|''D. laevigata'']], [[Digitalis nervosa|''D. nervosa'']], [[Digitalis ferruginea|''D. ferruginea'']], [[Digitalis cariensis|''D. cariensis'']] and [[Digitalis lanata|''D. lanata'']].
*''Tubiflorae'' included four species: ''D. subalpina'', [[Digitalis lutea|''D. lutea'']], [[Digitalis viridiflora|''D. viridiflora'']] and [[Digitalis parviflora|''D. parviflora'']].

In their 2000 book about ''Digitalis'', Luckner and Wichtl continued to uphold Werner's classification of the 19 species,<ref name=Wichtl2001/><ref name=Kreis2017/><ref>{{cite book |last1=Luckner |first1=M. |last2=Wichtl |first2=Max |date=2000 |title=''Digitalis'': Geschichte, Biologie, Chemie, Physiologie, Molekularbiologie, medizinische Anwendung. Handbuch für Ärzte, Apotheker und andere Naturwissenschaftler |location=Stuttgart |publisher=Wissenschaftliche Verlagsgesellschaft |language=de |isbn=3-8047-1705-5}}</ref> but molecular studies into the [[phylogeny]] of the genus published in 2004 found that although four of Werner's sections were supported by the genetics, the section ''Tubiflorae'' was [[polyphyletic]], and that the species ''D. lutea'' and ''D. viridiflora'' should be placed in the section ''Grandiflorae''.<ref name=Bräuchler2004>{{cite journal |last1=Bräuchler |first1=C. |last2=Meimberg |first2=H. |last3=Heubl |first3=G. |date=2004 |title=Molecular phylogeny of the genera ''Digitalis'' L. and ''Isoplexis'' (Lindley) Loudon (Veronicaceae) based on ITS- and trnL-F sequences |journal=Plant Systematics and Evolution |volume=248 |issue=1–4 |pages=111–128 |doi=10.1007/s00606-004-0145-z|bibcode=2004PSyEv.248..111B |s2cid=25480255 }}</ref> This study, as well as a number of other studies published around that time, reunited the genus ''Isoplexis'' with ''Digitalis'', increasing the number of species to 23.<ref name=Kreis2017/><ref name=Bräuchler2004/>

[[Peter Hadland Davis]], an expert on the flora of [[Turkey]], had used a different [[Circumscription (taxonomy)|circumscription]] than Werner in his works, and recognised eight species in the country. A 2016 molecular phylogenetic study into the relationships of the Turkish species in the section ''Globiflorae'' aimed to reconcile this discrepancy, finding that the classification as proposed by Davis was largely correct: ''Globiflorae'' contained as distinct species ''D. cariensis'', ''D. ferruginea'', ''D. lamarckii'', ''D. lanata'' and ''D. nervosa'', and ''D. trojana'' was subsumed at the infraspecific rank as ''D. lanata'' subsp. ''trojana''. This study listed 23 species: ''D. transiens'', ''D. cedretorum'', ''D. ikarica'' and ''D. fuscescens'' were not mentioned. ''D. parviflora'' and ''D. subalpina'' were not tested in this study,<ref name=Eker2016/> but the 2004 study found these two species situated within the section ''Globiflorae''.<ref name=Bräuchler2004/>

==Ecology==
[[File:Digitalis purpurea patch in Seattle.jpg|thumb|A patch of ''[[Digitalis purpurea]]'' in Seattle]]
[[Larva]]e of the [[foxglove pug]], a moth, consume the flowers of the common foxglove for food. Other species of [[Lepidoptera]] eat the leaves, including the [[lesser yellow underwing]].<ref name=HOSTS>{{cite journal|url=https://www.nhm.ac.uk/our-science/data/hostplants/search/list.dsml?searchPageURL=index.dsml&Familyqtype=starts+with&Family=&PFamilyqtype=starts+with&PFamily=&Genusqtype=contains&Genus=&PGenusqtype=starts+with&PGenus=digitalis&Speciesqtype=starts+with&Species=&PSpeciesqtype=starts+with&PSpecies=&Country=&sort=Family |last1=Robinson |first1=G. S. |last2=Ackery |first2=P. R. |last3=Kitching |first3=I. J. |last4=Beccaloni |first4=G. W. |last5=Hernández |first5=L. M. |title=''Digitalis'' |date=2010 |website=HOSTS – A Database of the World's Lepidopteran Hostplants |publisher=[[Natural History Museum, London]] |doi=10.5519/havt50xw |access-date=28 November 2020}}</ref> The shape of the foxglove's flowers makes it especially attractive to long-tongued bees, such as the [[Bombus pascuorum|common carder bee]].  The bright flowers attract the bee, which lands on the lower lip of the bloom before climbing up the tube. This means that the bee is likely to drop any pollen it may have collected from other foxgloves, thereby facilitating propagation.<ref>{{Cite web |last=Trust |first=Woodland |title=Foxglove (Digitalis purpurea) – British Plants |url=https://www.woodlandtrust.org.uk/trees-woods-and-wildlife/plants/wild-flowers/foxglove/ |access-date=2024-06-04 |website=Woodland Trust |language=en-GB}}</ref>

==Uses==

===Historical uses===
[[Nicholas Culpeper]] included Foxglove in his 1652 herbal medicine guide, ''The English Physician''. He cited its use for healing wounds (both fresh and old), as a purgative, for "the King's Evil" ([[mycobacterial cervical lymphadenitis]]), for "the falling sickness" ([[epilepsy]]), and for "a scabby head".<ref>{{cite book |last1=Culpeper |first1=Nicholas |title=The English Physician, Etc |date=1652 |publisher=William Bentley |location=London |pages=97–98 |edition=1st |url=https://books.google.com/books?id=WuyUw_5Hd8cC&pg=RA1-PA173 |access-date=22 January 2023 |language=en}}</ref> There is no empirical evidence for these claims, and it is not used for these conditions in modern medicine, only for slowing excessive heart rate in certain circumstances and/or strengthening heart muscle contraction in heart failure.<ref>{{cite web |title=BNF (only available in the UK) |url=https://bnf.nice.org.uk/drugs/digoxin/#indications-and-dose |website=NICE |publisher=BMJ & Pharmaceutical Press |access-date=20 February 2023}}</ref>

===Medicinal uses===
Digitalis is an example of a drug derived from a plant that was formerly used by [[herbalist]]s; 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 considered to be inappropriate treatments.

A group of medicines extracted from foxglove plants are called [[digitalin]]. The use of ''[[Digitalis purpurea|D. purpurea]]'' extract containing [[cardiac glycoside]]s for the treatment of heart conditions was first described in the English-speaking medical literature by [[William Withering]], in 1785,<ref>{{cite book | first1 = William | last1 = Withering | url = https://books.google.com/books?id=VgIta49rzT4C&pg=PR3 | title = An Account of the Foxglove and some of its Medical Uses | location = Birmingham, England | publisher = M. Swinney | date = 1785 }}</ref><ref>{{Cite journal|last1=Goldthorp |first1=W. O. |title=Medical Classics: An Account of the Foxglove and Some of its Medicinal Uses by William Withering, published 1785|journal=British Medical Journal |year=2009 |volume=338 |pages=b2189 |doi=10.1136/bmj.b2189 |s2cid=72429441}}</ref><ref>{{cite book|last1=Simpson |first1=Beryl Brintnall |last2=Ogorzaly |first2=Molly Coner |title=Economic Botany |date=2001 |publisher=Mc Graw Hill |location=Boston |isbn=9780072909388 |page=529 |edition=3rd}}</ref> which is considered the beginning of modern therapeutics. In contemporary medicine, digitalis (usually [[digoxin]]) is obtained from ''D. lanata''.<ref name="Hollman">{{cite journal |last1=Hollman |first1=A. |title=Drugs for atrial fibrillation. Digoxin comes from ''Digitalis lanata'' | journal = BMJ (Clinical Research Ed.) | volume = 312 | issue = 7035 | pages = 912 | date = April 1996 | pmid = 8611904 | pmc = 2350584 | doi = 10.1136/bmj.312.7035.912 }}</ref><ref name=Weisse2010>{{cite journal |last1=Weisse |first1=Allen B. |date=January 2010 |title=A Fond Farewell to the Foxglove? The Decline in the Use of Digitalis |journal=Journal of Cardiac Failure |volume=16 |issue=1 |pages=45–48 |doi=10.1016/j.cardfail.2009.08.001 |pmid=20123317|doi-access=free }}</ref> 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 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. The main factor is the more recent introduction of several drugs shown in randomised controlled studies to improve outcomes in heart failure.<ref>{{cite web |last1=Anon. |title=Medications Used to Treat Heart Failure |url=https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/medications-used-to-treat-heart-failure |website=www.heart.org |publisher=American Heart Association |access-date=13 August 2020 |language=en}}</ref> Safety concerns regarding a proposed link between digoxin therapy and increased mortality seen in observational studies may have contributed to the decline in therapeutic use of digoxin, however a systematic review of 75 studies including four million patient years of patient follow-up showed that in properly designed randomised controlled studies, mortality was no higher in patients given digoxin than in those given placebo.<ref>{{cite journal |last1=Ziff |first1=Oliver J. |last2=Lane |first2=Deirdre A. |last3=Samra |first3=Monica |last4=Griffith |first4=Michael |last5=Kirchhof |first5=Paulus |last6=Lip |first6=Gregory Y. H. |last7=Steeds |first7=Richard P. |last8=Townend |first8=Jonathan |last9=Kotecha |first9=Dipak |title=Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data |journal=British Medical Journal |language=en |doi=10.1136/bmj.h4451 |date=30 August 2015 |volume=351 |pages=h4451 |pmid=26321114 |pmc=4553205 |s2cid=9995597}}</ref>

[[Romani people]] use foxglove to treat eczema.<ref>{{cite book|url=https://books.google.com/books?id=WAagnZNb0cAC&dq=gypsies+foxglove+eczema&pg=PA129|title=Dictionary of Plant Lore|page=129|isbn=978-0-08-054602-5 |last1=Watts |first1=D. C. |date=2 May 2007 |publisher=Elsevier }}</ref>

====Variations====
[[File:Foxglove - Digitalis purpurea.jpg|thumb|Digitalis purpurea -- light purple]]
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). This results in digoxin having a half-life of about one day (and increasing with impaired kidney function), whereas digitoxin's is about 7 days and not affected by kidney function. 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 sodium causes the Na/Ca exchanger to reverse potential, i.e., transition from pumping sodium into the cell in exchange for pumping calcium out of the cell, to 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.<ref>{{cite journal |doi=10.1016/0165-6147(85)90136-1 |title=Sodium ion and the cardiac actions of digitalis |journal=Trends in Pharmacological Sciences |year=1985 |pages=296–298 |volume=6 |last1=Akera |first1=Tai |last2=Brody |first2=Theodore M.}}</ref> Under normal physiological conditions, the cytoplasmic calcium used in cardiac contractions originates from the [[sarcoplasmic reticulum]], an intracellular organelle that stores 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 favour 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 can be used to slow the ventricular rate during [[atrial fibrillation]] (unless there's [[Wolff–Parkinson–White syndrome|an accessory pathway]], when it can paradoxically increase the heart rate).<ref>{{cite journal |last1=Fuster |first1=Valentin |last2=Rydén |first2=Lars E. |last3=Asinger |first3=Richard W. |last4=Cannom |first4=David S. |last5=Crijns |first5=Harry J. |last6=Frye |first6=Robert L. |last7=Halperin |first7=Jonathan L. |last8=Kay |first8=G. Neal |last9=Klein |first9=Werner W. |last10=Lévy |first10=Samuel |last11=McNamara |first11=Robert L. |last12=Prystowsky |first12=Eric N. |last13=Wann |first13=L. Samuel |last14=Wyse |first14=D. George |last15=Gibbons |first15=Raymond J. |last16=Antman |first16=Elliott M. |last17=Alpert |first17=Joseph S. |last18=Faxon |first18=David P. |last19=Fuster |first19=Valentin |last20=Gregoratos |first20=Gabriel |last21=Hiratzka |first21=Loren F. |last22=Jacobs |first22=Alice K. |last23=Russell |first23=Richard O. |last24=Smith |first24=Sidney C. |last25=Klein |first25=Werner W. |last26=Alonso-Garcia |first26=Angeles |last27=Blomström-Lundqvist |first27=Carina |last28=de Backer |first28=Guy |last29=Flather |first29=Marcus |last30=Hradec |first30=Jaromir |last31=Oto |first31=Ali |last32=Parkhomenko |first32=Alexander |last33=Silber |first33=Sigmund |last34=Torbicki |first34=Adam |title=ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology |journal=Circulation |date=23 October 2001 |volume=104 |issue=17 |pages=2118–2150 |doi=10.1161/circ.104.17.2118 |pmid=11673357 |language=en |issn=0009-7322|doi-access=free }}</ref> 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.<ref>{{Cite journal |date=1985-05-01 |title=Digitalis and the autonomic nervous system |journal=Journal of the American College of Cardiology |language=en |volume=5 |issue=5 |pages=35A–42A |doi=10.1016/S0735-1097(85)80461-7 |issn=0735-1097 |last1=Watanabe |first1=August M. |pmid=3886751|doi-access=free }}</ref><ref>{{Cite journal |last1=Tonkon |first1=M. J. |last2=Lee |first2=G. |last3=DeMaria |first3=A. N. |last4=Miller |first4=R. R. |last5=Mason |first5=D. T. |date=December 1977 |title=Effects of digitalis on the exercise electrocardiogram in normal adult subjects |url=https://pubmed.ncbi.nlm.nih.gov/923306/ |journal=Chest |volume=72 |issue=6 |pages=714–718|doi=10.1378/chest.72.6.714 |issn=0012-3692 |pmid=923306}}</ref>

===Molecular probes===
[[Digoxigenin]] (DIG) is a steroid found in the flowers and leaves of ''Digitalis'' species, and is extracted from ''D. lanata''. Digoxigenin can be used as a [[molecular probe]] to detect [[mRNA]] in situ and label DNA, RNA, and [[oligonucleotides]].<ref name="Glick2018">{{cite book|last=Glick |first=Bernard R. |title=Methods in Plant Molecular Biology and Biotechnology |url=https://books.google.com/books?id=u0paDwAAQBAJ&pg=PA183 |date=4 May 2018 |publisher=CRC Press |isbn=978-1-351-09139-8 |pages=183}}</ref> It can easily be attached to nucleotides such as [[uridine]] by chemical modifications. DIG molecules are often linked to nucleotides; DIG-labelled uridine can then be incorporated into RNA via ''[[in vitro]]'' [[transcription (genetics)|transcription]]. Once [[Nucleic acid hybridization|hybridisation]] occurs, RNA with the incorporated DIG-U can be detected with anti-DIG [[antibodies]] conjugated to [[alkaline phosphatase]]. To reveal the hybridised transcripts, a [[chromogen]] can be used which reacts with the alkaline phosphatase to produce a coloured precipitate.<ref>{{Cite journal |last1=Lauter |first1=Gilbert |last2=Söll |first2=Iris |last3=Hauptmann |first3=Giselbert |date=2011-07-04 |title=Two-color fluorescent in situ hybridization in the embryonic zebrafish brain using differential detection systems |journal=BMC Developmental Biology |language=en |volume=11 |issue=1 |page=43 |doi=10.1186/1471-213X-11-43 |doi-access=free |pmid=21726453 |pmc=3141750 |issn=1471-213X }}</ref>

==Toxicity==
{{Main|Digoxin poisoning}}
[[Image:Digitalis purpurea Koehler drawing.jpg|thumb|right|''Digitalis purpurea'' drawings by [[Köhler's Medicinal Plants|Franz Köhler]]]]

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 toxins can be absorbed via the skin<ref>{{Cite web|title=GRECIAN FOXGLOVE|url=https://www.mda.state.mn.us/plants/pestmanagement/weedcontrol/noxiouslist/foxglove|access-date=2021-07-01|publisher=Minnesota Department of Agriculture|language=en-us}}</ref> or ingestion.

Digitalis intoxication, known as ''digitalism'', results from an overdose of digitalis and can cause gastrointestinal, cardiac and neurological effects. The former include appetite loss, nausea, vomiting and diarrhoea; the cardiac symptoms include both [[tachycardia]], and [[bradycardia]] (either of which, if severe enough, can result in [[Syncope (medicine)|syncope]]—see below); and the neurological effects include fatigue, delirium, and rarely [[xanthopsia]] (jaundiced or yellow vision).<ref name=Lewis1998>{{cite book |last=Lewis |first=Robert Alan |title= Lewis Dictionary of Toxicology |date=1998 |page=387 |publisher=CRC Press |isbn=978-1-56670-223-2 |quote=Symptoms may include gastrointestinal disturbances and pain, severe headache, nausea, vomiting, diarrhea, irregular pulse, and yellow vision... }}</ref><ref>{{cite web |title=Digoxin Toxicity |url=https://www.rcemlearning.co.uk/foamed/digoxin-toxicity-2/ |website=RCEMLearning |access-date=20 February 2023}}</ref><ref>{{cite journal |last1=Renard |first1=D |last2=Rubli |first2=E |last3=Voide |first3=N |last4=Borruat |first4=FX |last5=Rothuizen |first5=LE |title=Spectrum of digoxin-induced ocular toxicity: a case report and literature review. |journal=BMC Research Notes |date=23 August 2015 |volume=8 |pages=368 |doi=10.1186/s13104-015-1367-6 |pmid=26298392 |pmc=4546820 |doi-access=free }}</ref> Other oculotoxic effects of digitalis include generalized blurry vision, as well as the appearance of blurred outlines ('halos').<ref>{{ cite book |last1=Goldfrank |first1=L. W. | title = Goldfrank's Toxicologic Emergencies | edition = 8th | location = New York | publisher = McGraw-Hill | year = 2006 }}</ref> Other things mentioned are dilated pupils, drooling, weakness, collapse, seizures, and even death.

Digitalis poisoning can cause indirect inhibition of the [[atrioventricular node]] via a direct effect on the [[Dorsal nucleus of vagus nerve|vagal nucleus]]. This results in [[bradycardia]] (decreased heart rate) or if severe enough, [[heart block]]. The direct effect of [[cardiac glycoside]]s on heart muscle cells is to increase contraction of the cells, both in force and frequency, tending to produce [[tachycardia]] (increased heart rate), depending on the dose, the condition of one's heart, and the prevailing chemistry of the blood (specifically any of: low potassium, high calcium and low magnesium).<ref>{{cite journal |last1=Rehman |first1=Rameez |last2=Dawson |first2=Andrew H. |last3=Hai |first3=Ofek |title=Digitalis Toxicity |url=https://www.ncbi.nlm.nih.gov/books/NBK459165/ |website=StatPearls |publisher=StatPearls Publishing |access-date=20 February 2023 |date=2022|pmid=29083729 }}</ref> Electrical cardioversion (to "shock" the heart) is generally not indicated in ventricular fibrillation in digitalis toxicity, as it can make the rhythm disturbance more complicated or sustained.<ref>{{Cite book|title=Mammalian Toxicology|last=Abou-Donia|first=Mohamed|publisher=John Wiley & Sons|year=2015|isbn=9781118683316|pages=631}}</ref><ref>{{cite journal |last1=Fuster |first1=Valentin |last2=Rydén |first2=Lars E. |last3=Cannom |first3=David S. |last4=Crijns |first4=Harry J. |last5=Curtis |first5=Anne B. |last6=Ellenbogen |first6=Kenneth A. |last7=Halperin |first7=Jonathan L. |last8=Le Heuzey |first8=Jean-Yves |last9=Kay |first9=G. Neal |last10=Lowe |first10=James E. |last11=Olsson |first11=S. Bertil |last12=Prystowsky |first12=Eric N. |last13=Tamargo |first13=Juan Luis |last14=Wann |first14=Samuel |title=ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive Summary |journal=Journal of the American College of Cardiology |date=August 2006 |volume=48 |issue=4 |page=861 |doi=10.1016/j.jacc.2006.07.009|pmid=16904574 |s2cid=8975477 |doi-access=free }}</ref> Furthermore, the classic drug of choice for ventricular fibrillation in emergency setting,<ref>{{cite web |url=http://www.erc.edu |title=European Resuscitation Council}}{{Verify source|date=December 2008}}</ref> [[amiodarone]], can worsen the dysrhythmia caused by digitalis, therefore, the second-choice drug [[lidocaine]] is more commonly used.<ref>{{Cite book|title=Back to Basics: Critical Care Transport Certification Review|last=Lee Lopez|first=Orchid|publisher=Xlibris Corporation|year=2011|isbn=9781456862749|pages=290}}</ref> Mild toxicity is treated by stopping the medication and general supportive measures; severe toxicity is treated with [[Digoxin immune fab|anti-digoxin antibody fragments]].

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 ingestion by adolescents and adults.<ref>{{cite web |url=http://emedicine.medscape.com/article/816781-overview#a0199 |title=Cardiac Glycoside Plant Poisoning: Medscape reference|access-date=3 July 2012}}</ref>

In some instances, people have confused foxglove with the relatively harmless comfrey (''[[Symphytum]]'') plant, which is sometimes brewed into a tea, with fatal consequences. Other fatal accidents involve children drinking the water in a vase containing digitalis plants.<ref>{{cite web|url=http://www.cbif.gc.ca/pls/pp/ppack.info?p_psn=57&p_type=all&p_sci=sci |title=Notes on poisoning:''Digitalis purpura'' |last=Anon |work=Canadian poisonous plants information system |publisher=Canadian Biodiversity Information Facility |access-date=9 March 2013 |url-status=dead |archive-url=https://web.archive.org/web/20111013203513/http://www.cbif.gc.ca/pls/pp/ppack.info?p_psn=57&p_type=all&p_sci=sci |archive-date=13 October 2011}}</ref> 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.

==In popular culture==
According to 1981 speculation, [[Vincent van Gogh]]'s "Yellow Period" may have been influenced by digitalis, because it had been proposed as a therapy to control epilepsy around this time, and there are two paintings by the artist where the plant is present.<ref>{{cite journal |last1=Lee |first1=T. C. |date=20 February 1981 |title=Van Gogh's vision. ''Digitalis'' intoxication? |journal=JAMA |volume=245 |issue=7 |pages=727–729 |doi=10.1001/jama.1981.03310320049025 |pmid=7007674}}</ref> Other studies immediately questioned this: there are a large number of other possible explanations for van Gogh's choice of palette,<ref>{{cite journal |last1=Lanthony |first1=P. |date=October 1989 |title=[Van Gogh's xanthopsia] |journal=Bulletin des Sociétés d'Ophtalmologie Française |volume=89 |issue=10 |pages=1133–1134 |language=fr |pmid=2695267}}</ref><ref name=Arnold1991>{{cite journal |last1=Arnold |first1=Wilfred Niels |last2=Loftus |first2=Loretta S. |date=1 September 1991 |title=Xanthopsia and van Gogh's yellow palette |url=https://www.nature.com/articles/eye199193.pdf |archive-url=https://web.archive.org/web/20181030071440/https://www.nature.com/articles/eye199193.pdf |archive-date=2018-10-30 |url-status=live |journal=Eye |volume=5 |issue=5 |pages=503–510 |doi=10.1038/eye.1991.93 |pmid=1794418 |s2cid=26723081 |access-date=28 November 2020|doi-access=free }}</ref> there is no evidence that van Gogh was ever given the drug or that his physician prescribed it, he was tested and had no [[xanthopsia]], and in his many letters of the time he makes it clear that he simply liked using the colour yellow,<ref name=Arnold1991/><ref name=Gruener2013>{{cite journal |last1=Gruener |first1=Anna |date=July 2013 |title=Vincent van Gogh's yellow vision |url=https://bjgp.org/content/63/612/370.long |journal=British Journal of General Practice |volume=63 |issue=612 |pages=370–371 |pmid=23834871 |pmc=3693787 |doi=10.3399/bjgp13X669266 |access-date=28 November 2020}}</ref><ref>{{cite journal |last1=Voskuil |first1=Piet |date=October 2020 |title=Vincent van Gogh and his illness. A reflection on a posthumous diagnostic exercise |journal=  Epilepsy & Behavior|volume=111 |issue=107258 |page=107258 |pmid=32629415 |doi=10.1016/j.yebeh.2020.107258|s2cid=220323719 }}</ref> but it has remained a popular theory.<ref>{{cite news |last=Harkup |first=Kathryn |authorlink=Kathryn Harkup|date=10 August 2017 |title=It was all yellow: did digitalis affect the way Van Gogh saw the world? |url=https://www.theguardian.com/science/blog/2017/aug/10/it-was-all-yellow-did-digitalis-affect-the-way-van-gogh-saw-the-world |work=The Guardian (UK) |access-date=28 November 2020}}</ref>

==References==
{{Reflist}}

==External links==
{{Commons|2=''Digitalis''}}
{{Wiktionary|digitalis}}
{{EB1911 poster|Digitalis}}
*[http://www.bris.ac.uk/Depts/Chemistry/MOTM/digitalis/digtalis.htm Molecule of the Month – Digitalis]
*[http://www.emedicine.com/PED/topic590.htm eMedicine link]
*{{Cite Collier's|wstitle=Foxglove|year=1921 |short=x}}

{{Taxonbar|from=Q156533}}
{{Authority control}}

[[Category:Digitalis| ]]
[[Category:Plantaginaceae genera]]
[[Category:Antiarrhythmic agents]]
[[Category:Medicinal plants]]