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''Digitalis'' ( or ) is a
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...
of about 20
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
of
herbaceous Herbaceous plants are vascular plants that have no persistent woody stems above ground. This broad category of plants includes many perennials, and nearly all annuals and biennials. Definitions of "herb" and "herbaceous" The fourth edition o ...
perennial plant A perennial plant or simply perennial is a plant that lives more than two years. The term ('' per-'' + '' -ennial'', "through the years") is often used to differentiate a plant from shorter-lived annuals and biennials. The term is also wide ...
s,
shrub A shrub (often also called a bush) is a small-to-medium-sized perennial woody plant. Unlike herbaceous plants, shrubs have persistent woody stems above the ground. Shrubs can be either deciduous or evergreen. They are distinguished from tree ...
s, and
biennials A biennial plant is a flowering plant that, generally in a temperate climate, takes two years to complete its biological life cycle. Life cycle In its first year, the biennal plant undergoes primary growth, during which its vegetative structures ...
, 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 scientific name means "finger". The genus was traditionally placed in the figwort
family Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...
,
Scrophulariaceae The Scrophulariaceae are a family of flowering plants, commonly known as the figwort family. The plants are annual and perennial herbs, as well as shrubs. Flowers have bilateral (zygomorphic) or rarely radial (actinomorphic) symmetry. The Scr ...
, but
phylogenetic In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups ...
research led taxonomists to move it to the Veronicaceae in 2001. 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 Ornamental plants or garden plants are plants that are primarily grown for their beauty but also for qualities such as scent or how they shape physical space. Many flowering plants and garden varieties tend to be specially bred cultivars that ...
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''. The term ''digitalis'' is also used for drug preparations that contain cardiac glycosides, particularly one called
digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is o ...
, extracted from various plants of this genus. Foxglove has medicinal uses but is also very toxic to humans and other animals, and consumption can even lead to death.


Etymology

The generic epithet ''Digitalis'' is from the
Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through ...
''digitus'' (finger).
Leonhart Fuchs Leonhart Fuchs (; 17 January 1501 – 10 May 1566), sometimes spelled Leonhard Fuchs and cited in Latin as ''Leonhartus Fuchsius'', was a German physician and botanist. His chief notability is as the author of a large book about plants and th ...
first invented the name for this plant in his 1542 book ''De historia stirpium commentarii insignes'', based upon the German
vernacular name A vernacular or vernacular language is in contrast with a "standard language". It refers to the language or dialect that is spoken by people that are inhabiting a particular country or region. The vernacular is typically the native language, n ...
''Fingerhut'', which translates literally as 'finger hat', but actually means ' thimble'. The name is recorded in
Old English Old English (, ), or Anglo-Saxon, is the earliest recorded form of the English language, spoken in England and southern and eastern Scotland in the early Middle Ages. It was brought to Great Britain by Anglo-Saxon settlers in the mid-5th ...
as 'foxes glofe/glofa' or 'fox's glove'. 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.
Henry Fox Talbot William Henry Fox Talbot FRS FRSE FRAS (; 11 February 180017 September 1877) was an English scientist, inventor, and photography pioneer who invented the salted paper and calotype processes, precursors to photographic processes of the later 1 ...
(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''.


Taxonomy


Species

The ''
Flora Europaea The ''Flora Europaea'' is a 5-volume encyclopedia of plants, published between 1964 and 1993 by Cambridge University Press. The aim was to describe all the national Floras of Europe in a single, authoritative publication to help readers identify ...
'' originally recognised a number of species now seen as synonyms of ''Digitalis purpurea'', or others: ''D. dubia'', ''D. leucophaea'', ''D. micrantha'' and ''D. trojana''. As of 2017, ''
Plants of the World Online Plants of the World Online (POWO) is an online database published by the Royal Botanic Gardens, Kew. It was launched in March 2017 with the ultimate aim being "to enable users to access information on all the world's known seed-bearing plants by ...
'' recognises the following 27 species (and a number of hybrids): *'' Digitalis atlantica'' Pomel *''
Digitalis canariensis ''Digitalis canariensis'' is a member of the genus ''Digitalis''. Taxonomy This species is part of section '' Isoplexis'', which was temporarily accepted as an own genus. The synonym ''Isoplexis canariensis'' also continues to be used. In genera ...
'' L. *'' Digitalis cariensis'' Boiss. ex Jaub. & Spach *'' Digitalis cedretorum'' ( Emb.) Maire *'' Digitalis chalcantha'' ( Svent. & O'Shan.) Albach, Bräuchler & Heubl *'' Digitalis ciliata'' Trautv. *'' Digitalis davisiana'' Heywood *'' Digitalis ferruginea'' L. *'' Digitalis fuscescens'' Waldst. & Kit. *''
Digitalis grandiflora ''Digitalis grandiflora'', the yellow foxglove, big-flowered foxglove, or large yellow foxglove, is a species of flowering plant in the genus ''Digitalis'', family Plantaginaceae (formerly Scrophulariaceae). It is native to southern Europe and As ...
'' Mill. *'' Digitalis ikarica'' ( P.H.Davis) Strid *'' Digitalis isabelliana'' (Webb) Linding. *'' Digitalis laevigata'' Waldst. & Kit. *'' Digitalis lamarckii'' Ivanina *'' Digitalis lanata''
Ehrh. Jakob Friedrich Ehrhart (4 November 1742, Holderbank, Aargau – 26 June 1795) was a German botanist, a pupil of Carl Linnaeus at Uppsala University, and later director of the Botanical Garden of Hannover, where he produced several major botanic ...
*''
Digitalis lutea ''Digitalis lutea'', the straw foxglove or small yellow foxglove, is a species of flowering plant in the plantain family (botany), family Plantaginaceae, that is native species, native to western and southern Europe and North West Africa. A shor ...
'' L. *''
Digitalis mariana ''Digitalis mariana'' is a flowering plant species in the family Plantaginaceae. It is a perennial foxglove with evergreen foliage and rose-red coloured flowers produced in summer. It is native to Portugal and Spain. Taxonomy ''Digitalis mariana ...
'' Boiss. *'' Digitalis minor'' L. *'' Digitalis nervosa'' Steud. & Hochst. ex
Benth. George Bentham (22 September 1800 – 10 September 1884) was an English botanist, described by the weed botanist Duane Isely as "the premier systematic botanist of the nineteenth century". Born into a distinguished family, he initially studie ...
*'' Digitalis obscura'' L. *'' Digitalis parviflora''
Jacq. Nikolaus Joseph Freiherr von Jacquin (16 February 172726 October 1817) was a scientist who studied medicine, chemistry and botany. Biography Born in Leiden in the Netherlands, he studied medicine at Leiden University, then moved first to Par ...
*'' Digitalis purpurea'' L. *'' Digitalis sceptrum'' L.f. *'' Digitalis subalpina'' Braun-Blanq. *'' Digitalis thapsi'' L. *'' Digitalis transiens'' Maire *''
Digitalis viridiflora ''Digitalis viridiflora'' is a species of flowering plant commonly called green foxglove in Family (taxonomy), family Plantaginaceae. It is a perennial species with greenish-yellow flowers produced on stems that grow 60 to 80cm tall. It is native ...
''
Lindl. John Lindley FRS (5 February 1799 – 1 November 1865) was an English botanist, gardener and orchidologist. Early years Born in Catton, near Norwich, England, John Lindley was one of four children of George and Mary Lindley. George Lindley ...


Hybrids

*'' Digitalis × coutinhoi'' Samp. *''
Digitalis × fulva ''Digitalis'' × ''fulva'', the strawberry foxglove, is a fertile hybrid between ''Digitalis grandiflora'' and ''Digitalis purpurea''. Description This perennial herbaceous plant reaches an average a height of . The erect stems rise from a semi- ...
'' Lindl. *'' Digitalis × macedonica'' Heywood *'' Digitalis × media'' Roth *'' Digitalis × pelia'' Zerbst & Bocquet *'' Digitalis × purpurascens'' Roth *''Digitalis'' × ''sibirica'' (Lindley) Werner had been considered a valid species since it was first described by the English botanist and gardener
John Lindley John Lindley FRS (5 February 1799 – 1 November 1865) was an English botanist, gardener and orchidologist. Early years Born in Catton, near Norwich, England, John Lindley was one of four children of George and Mary Lindley. George Lindley w ...
in 1821, but it was considered a hybrid of ''D. grandiflora'' and ''D. laevigata'' by the German botanist in 1960.


Systematics

The first full
monograph A monograph is a specialist work of writing (in contrast to reference works) or exhibition on a single subject or an aspect of a subject, often by a single author or artist, and usually on a scholarly subject. In library cataloging, ''monogra ...
regarding this genus was written by Lindley in 1821. He included two sections, a section ''
Isoplexis {{Italic title ''Isoplexis'' is a section of four species of flowering plants within the genus ''Digitalis'' in the plantain family Plantaginaceae. The species of section ''Isoplexis'' differ from other plants in the genus ''Digitalis'' in t ...
'' including two species, and the main section ''Digitalis'' with three subsections, including 2Y species, a number of which are now seen as
synonyms A synonym is a word, morpheme, or phrase that means exactly or nearly the same as another word, morpheme, or phrase in a given language. For example, in the English language, the words ''begin'', ''start'', ''commence'', and ''initiate'' are ...
or hybrids. In the last full monograph of the genus in 1965, Werner classified the 19 recognised species in five
sections Section, Sectioning or Sectioned may refer to: Arts, entertainment and media * Section (music), a complete, but not independent, musical idea * Section (typography), a subdivision, especially of a chapter, in books and documents ** Section sig ...
(four species from
Macaronesia Macaronesia (Portuguese: ''Macaronésia,'' Spanish: ''Macaronesia'') is a collection of four volcanic archipelagos in the North Atlantic, off the coasts of Africa and Europe. Each archipelago is made up of a number of Atlantic oceanic islands ...
were separated in the genus ''Isoplexis'' at the time): *In the section ''Digitalis'', along with the
type species In zoological nomenclature, a type species (''species typica'') is the species name with which the name of a genus or subgenus is considered to be permanently taxonomically associated, i.e., the species that contains the biological type specim ...
''D. purpurea'', four other species (as recognised as the time) were placed: ''D. thapsi'', ''D. dubia'', ''D. heywoodii'' and ''D. mariana''. *The
monotypic In biology, a monotypic taxon is a taxonomic group (taxon) that contains only one immediately subordinate taxon. A monotypic species is one that does not include subspecies or smaller, infraspecific taxa. In the case of genera, the term "unispe ...
section ''Frutescentes'' contained only ''D. obscura''. *The section ''Grandiflorae'', which was also called section ''Macranthae'' by Vernon Hilton Heywood. It included, along with the
type species In zoological nomenclature, a type species (''species typica'') is the species name with which the name of a genus or subgenus is considered to be permanently taxonomically associated, i.e., the species that contains the biological type specim ...
''D. grandiflora'', also ''D. atlantica'', ''D. ciliata'' and ''D. davisiana''. *''Globiflorae'' included five species: ''D. laevigata'', ''D. nervosa'', ''D. ferruginea'', ''D. cariensis'' and ''D. lanata''. *''Tubiflorae'' included four species: ''D. subalpina'', ''D. lutea'', ''D. viridiflora'' and ''D. parviflora''. In their 2000 book about ''Digitalis'', Luckner and Wichtl continued to uphold Werner's classification of the 19 species, but molecular studies into the
phylogeny A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological s ...
of the genus published in 2004 found that although four of Werner's sections were supported by the genetics, the section ''Tubiflorae'' was
polyphyletic A polyphyletic group is an assemblage of organisms or other evolving elements that is of mixed evolutionary origin. The term is often applied to groups that share similar features known as homoplasies, which are explained as a result of conver ...
, and that the species ''D. lutea'' and ''D. viridiflora'' should be placed in the section ''Grandiflorae''. 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. Peter Hadland Davis, an expert on the flora of
Turkey Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a transcontinental country located mainly on the Anatolian Peninsula in Western Asia, with a small portion on the Balkan Peninsula ...
, had used a different 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, but the 2004 study found these two species situated within the section ''Globiflorae''.


Ecology

Larva A larva (; plural larvae ) is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle. ...
e of the foxglove pug, a moth, consume the flowers of the common foxglove for food. Other species of
Lepidoptera Lepidoptera ( ) is an order of insects that includes butterflies and moths (both are called lepidopterans). About 180,000 species of the Lepidoptera are described, in 126 families and 46 superfamilies, 10 percent of the total described speci ...
eat the leaves, including the
lesser yellow underwing The lesser yellow underwing (''Noctua comes'') is a moth of the family Noctuidae. Distribution It is found in the Palearctic realm ( Europe, North Africa, Canary Islands, Middle East, South Russia, Caucasus, Transcaucasia, Turkey, Iraq, ...
.


Uses


Cardiac

Digitalis is an example of a drug derived from a plant that was formerly used by herbalists; herbalists have largely abandoned its use because of its narrow
therapeutic index The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
and the difficulty of determining the amount of active drug in herbal preparations. Once the usefulness of digitalis in regulating the human
pulse In medicine, a pulse represents the tactile arterial palpation of the cardiac cycle (heartbeat) by trained fingertips. The pulse may be palpated in any place that allows an artery to be compressed near the surface of the body, such as at the n ...
was understood, it was employed for a variety of purposes, including the treatment of
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...
and other seizure disorders, which are now considered to be inappropriate treatments. A group of medicines extracted from foxglove plants are called
digitalin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is o ...
. The use of '' D. purpurea'' extract containing cardiac glycosides for the treatment of
heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...
conditions was first described in the English-speaking medical literature by
William Withering William Withering FRS (17 March 1741 – 6 October 1799) was an English botanist, geologist, chemist, physician and first systematic investigator of the bioactivity of digitalis. Withering was born in Wellington, Shropshire, the son of a surg ...
, in 1785, which is considered the beginning of modern therapeutics. In contemporary
medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...
digitalis (usually
digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is o ...
) is obtained from ''D. lanata''. It is used to increase cardiac contractility (it is a positive inotrope) and as an
antiarrhythmic agent Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms ( tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular ta ...
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 Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
. 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 The Heart Failure Society of America is an American organization of heart failure experts who have an interest in heart function and heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of sig ...
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. 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.


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 Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, though the effects are longer-lasting. Unlike digoxin, wh ...
or
digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is o ...
, or by brand names such as Crystodigin and Lanoxin, respectively. The two drugs differ in that digoxin has an additional
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...
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 Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or do ...
called a
glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...
.


Mechanism of action

Digitalis works by inhibiting sodium-potassium ATPase. This results in an increased intracellular concentration of
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...
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. Under normal physiological conditions, the cytoplasmic calcium used in cardiac contractions originates from the
sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...
, 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 The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part o ...
, and as such is used in re-entrant
cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...
s 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 The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...
drive, which is the case with acutely ill persons, and also during exercise.


Digoxigenin

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 molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
in situ and label DNA, RNA, and oligonucleotides. 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 ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' transcription. Once hybridisation occurs, RNA with the incorporated DIG-U can be detected with anti-DIG
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
conjugated to
alkaline phosphatase The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...
. To reveal the hybridised transcripts, a
chromogen In chemistry, the term chromogen refers to a colourless (or faintly coloured) chemical compound that can be converted by chemical reaction into a compound which can be described as "coloured". There is no universally agreed definition of the term. ...
can be used which reacts with the alkaline phosphatase to produce a coloured precipitate.


Toxicity

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. Digitalis intoxication, known as ''digitalism'', results from an overdose of digitalis and causes gastrointestinal disturbances and pain, severe headache,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...
and
diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
,
cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...
s, as well as sometimes resulting in
xanthopsia Xanthopsia is a color vision deficiency in which there is a dominantly yellow bias in vision due to a yellowing of the optical media of the eye. The most common causes are digoxin's inhibitory action on the sodium pump, and the development of catar ...
(jaundiced or yellow vision). The toxins can be absorbed via the skin or ingestion; early symptoms of digitalism include nausea, vomiting, diarrhoea, abdominal pain, wild hallucinations,
delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances ...
, and severe headache. Depending on the severity of the toxicosis, the victim may later suffer irregular and slow pulse,
tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...
s, various cerebral disturbances, especially of a visual nature (unusual colour visions (see
xanthopsia Xanthopsia is a color vision deficiency in which there is a dominantly yellow bias in vision due to a yellowing of the optical media of the eye. The most common causes are digoxin's inhibitory action on the sodium pump, and the development of catar ...
) with objects appearing yellowish to green, and blue halos around lights),
convulsions A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a ...
, and deadly disturbances of the heart. Other oculotoxic effects of digitalis include generalized blurry vision, as well as the appearance of blurred outlines ('halos'). Other things mentioned are dilated pupils, drooling, weakness, collapse, seizures, and even death. Because a frequent side effect of digitalis is reduction of appetite, some individuals have used the drug as a weight-loss aid. Digitalis poisoning can cause heart block and either
bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, ...
(decreased heart rate) or
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
(increased heart rate), depending on the dose and the condition of one's heart. The electric cardioversion (to "shock" the heart) is generally not indicated in ventricular fibrillation in digitalis toxicity, as it can increase the dysrhythmia. Furthermore, the classic drug of choice for ventricular fibrillation in emergency setting, amiodarone, can worsen the dysrhythmia caused by digitalis, therefore, the second-choice drug
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lid ...
is more commonly used. 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. 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. 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.


Trivia

According to 1981 speculation
Vincent van Gogh Vincent Willem van Gogh (; 30 March 185329 July 1890) was a Dutch Post-Impressionist painter who posthumously became one of the most famous and influential figures in Western art history. In a decade, he created about 2,100 artworks, inc ...
'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. Other studies immediately questioned this: there are a large number of other possible explanations for van Gogh's choice of palette, 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, but it has remained a popular concept.


References


External links


Molecule of the Month - Digitalis
* {{Authority control Plantaginaceae genera Antiarrhythmic agents Medicinal plants Poisonous plants