Digitalis (pronounced /ˌdɪdʒɨˈteɪlɨs/^[2] or /ˌdɪdʒɨˈtælɨs/^[3]) is a genus of about 20 species of herbaceous In American English the initial "h" is normally silent: /ˈɜrb/.[Full citation needed] In standard British English the "h" is pronounced: /ˈhɜːb/ Also see American and British English pronunciation differences. In Canada, it is pronounced either with or without the "h" perennials A perennial plant or perennial is a plant that lives for more than two years. When used by gardeners or horticulturalists, applies specifically to winter hardy perennial herbaceous plants. Scientifically, woody plants like shrubs and trees are also perennial in their habit, shrubs, and biennials A biennial plant is a flowering plant that takes two years to complete its biological lifecycle. In the first year the plant grows leaves, stems, and roots , then it enters a period of dormancy over the colder months. Usually the stem remains very short and the leaves are low to the ground, forming a rosette. Many biennials require a cold that are commonly called foxgloves. This genus was traditionally placed in the figwort family Scrophulariaceae Scrophulariaceae, the figwort family, is a family of flowering plants. The plants are annual or perennial herbs with flowers with bilateral or rarely radial (actinomorphic) symmetry. Members of the Scrophulariaceae have a cosmopolitan distribution, with the majority found in temperate areas, including tropical mountains. The family name is based, but upon recent reviews of phylogenetic In biology, phylogenetics is the study of evolutionary relatedness among various groups of organisms , which is discovered through molecular sequencing data and morphological data matrices. The term phylogenetics is of Greek origin from the terms phyle/phylon (φυλή/φῦλον), meaning "tribe, race," and genetikos (γενετικός research, it has now been placed in the much enlarged family Plantaginaceae The Plantaginaceae Juss. or plantain family, is a family of flowering plants in the order Lamiales. The type genus is Plantago L..^[1] This genus is native to western and south western Europe,^[4] western and central Asia, and northwestern Africa. The scientific name means "finger-like" and refers to the ease with which a flower A flower, sometimes known as a bloom or blossom, is the reproductive structure found in flowering plants . The biological function of a flower is to mediate the union of male sperm with female ovum in order to produce seeds. The process begins with pollination, is followed by fertilization, leading to the formation and dispersal of the seeds. For 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 Digitalis purpurea , is a flowering plant in the family Plantaginaceae (formerly treated in the family Scrophulariaceae), native to most of Europe. This is a biennial plant A biennial plant is a flowering plant that takes two years to complete its biological lifecycle. In the first year the plant grows leaves, stems, and roots , then it enters a period of dormancy over the colder months. Usually the stem remains very short and the leaves are low to the ground, forming a rosette. Many biennials require a cold which is often grown as an ornamental plant Ornamental plants or garden plants are typically grown in the flower garden or as house plants. Most commonly they are grown for the display of their flowers. Other common ornamental features include leaves, scent, fruit, stem and bark. In some cases, unusual features may be considered ornamental, such as the prominent and rather vicious thorns of due to its vivid flowers A flower, sometimes known as a bloom or blossom, is the reproductive structure found in flowering plants . The biological function of a flower is to mediate the union of male sperm with female ovum in order to produce seeds. The process begins with pollination, is followed by fertilization, leading to the formation and dispersal of the seeds. For. These range in color from various purple tints In color theory, a tint is the mixture of a color with white, which increases lightness, and a shade is the mixture of a color with black, which reduces lightness. Mixing with any neutral color, including black and white, reduces chroma or colorfulness, while the hue remains unchanged through various shades of light gray, and to purely white. The flowers can also possess various marks and spottings.

The first year of growth of the Common Foxglove 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 250 centimeters A centimetre is a unit of length in the metric system, equal to one hundredth of a metre, which is the current SI base unit of length. Centi is the SI prefix for a factor of 10−2. Hence a centimetre can be written as 10 × 10−3 m (engineering notation) or 1E−2 m (scientific E notation) — meaning 10 × 101 mm or 1 m/100 respectively. The tall grows atop the roots of healthy plants.

The larvae A larva 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 of the insect the "Foxglove pug" consume the flowers of the Common Foxglove for food. Other species of Lepidoptera Lepidoptera is a large order of insects that includes moths and butterflies (called lepidopterans). It is one of the most speciose orders in the world, encompassing moths and the three superfamilies of butterflies, skipper butterflies, and moth-butterflies and found virtually everywhere. Lepidoptera contains more than 180,000 species in 128 eat the leaves of the Common Foxglove, including Lesser Yellow Underwing.

The term digitalis is also used for drug A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage preparations that contain cardiac glycosides Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals, particularly one called digoxin Digoxin (pronounced /dɨˈdʒɒksɨn/), also known as digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter, that are extracted from various plants of this genus.

Etymology

There have been many suggestions for the derivation of the name "foxglove". According to the 19th century book, English Botany, Or, Coloured Figures of British Plants:

Dr. Prior, whose authority is great in the origin of popular names, says "It seems probably that the name was in the first place, foxes' glew, or music, in reference to the favourite instrument of an earlier time, a ring of bells hung on an arched support, the tintinnabulum"... we cannot quite agree with Dr. Prior for it seems quite probable that the shape of the flowers suggested the idea of a glove, and that associated with the name of the botanist Fuchs, who first gave it a botanical name, may have been easily corrupted into foxglove. It happens, moreover, the name foxglove is a very ancient one and exists in a list of plants as old as the time of Edward III. The "folks" of our ancestors were the fairies and nothing is more likely than that the pretty coloured bells of the plant would be designated "folksgloves," afterwards, "foxglove." In Wales it is declared to be a favourite lurking-place of the fairies, who are said to occasion a snapping sound when children, holding one end of the digitalis bell, suddenly strike the other on the hand to hear the clap of fairy thunder, with which the indignant fairy makes her escape from her injured retreat. In south of Scotland it is called "bloody fingers" more northward, "deadman's bells" whilst in Wales it is known as "fairy-folks-fingers" or "lambs-tongue-leaves."^[5]

Habitat

Digitalis thrives 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 hedgebanks.^[4][6] It is commonly found on sites where the ground has been disturbed, such as recently cleared woodland, or where the vegetation has been burnt.^[7]

Medicinal use

A group of medicines extracted from foxglove plants are called "Digitalin". The use of Digitalis purpurea Digitalis purpurea , is a flowering plant in the family Plantaginaceae (formerly treated in the family Scrophulariaceae), native to most of Europe extract containing cardiac glycosides Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals for the treatment of heart The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions. The term cardiac (as in cardiology) means "related to the heart" and comes from the Greek καρδιά, kardia, for "heart." conditions was first described in the English speaking medical literature by William Withering, in 1785,^[8] which is considered the beginning of modern therapeutics (Silverman)^[9][10] It is used to increase cardiac contractility (it is a positive inotrope An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction) and as an antiarrhythmic agent Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress fast rhythms of the heart , such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation to control the heart rate, particularly in the irregular (and often fast) atrial fibrillation Atrial fibrillation is the most common cardiac arrhythmia (abnormal heart rhythm) and involves the two upper chambers (atria) of the heart. Its name comes from the fibrillating (i.e. quivering) of the heart muscles of the atria, instead of a coordinated contraction. It can often be identified by taking a pulse and observing that the heartbeats don'. Digitalis is hence often prescribed for patients in atrial fibrillation, especially if they have been diagnosed with congestive heart failure Heart failure is a condition in which a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. The phrase is often incorrectly used to describe other cardiac-related illnesses, such as myocardial infarction (heart attack) or cardiac arrest.

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 Digoxin (pronounced /dɨˈdʒɒksɨn/), also known as digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter, or by brand names such as Crystodigin and Lanoxin, respectively. The two drugs differ in that Digoxin has an additional hydroxyl In chemistry, hydroxyl is a compound containing an oxygen atom bound covalently with a hydrogen atom. The neutral form of this group is a hydroxyl radical. The hydroxyl anion is called hydroxide; it is a diatomic ion with a single negative electronic charge. In discussions of synthetic methods in organic chemistry the hydroxyl group (–OH) is group at the C-3 position on the B-ring (adjacent to the pentane). Both molecules include a lactone In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule. It is characterized by a closed ring consisting of two or more carbon atoms and a single oxygen atom, with a ketone group =O in one of the carbons adjacent to the latter and a triple-repeating sugar Sugar is an informal term for a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose characterized by a sweet flavor. In food, sugar almost exclusively refers to sucrose, which primarily comes from sugar cane and sugar beet. Other sugars are used in industrial food preparation, but are usually known by more specific called a glycoside In chemistry, glycosides are molecules in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme hydrolysis, which causes the sugar part to be broken off,.

Digitalis works by inhibiting sodium-potassium ATPase. This results in an increased intracellular concentration of sodium, which in turn increases intracellular calcium Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust. Calcium is also the fifth most abundant dissolved ion in seawater by both molarity and mass, after sodium, chloride, by passively decreasing the action of the sodium-calcium exchanger The sodium-calcium exchanger is an antiporter membrane protein which removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions (Ca2+). The NCX removes a single calcium ion in in the sarcoplasmic reticulum The endoplasmic reticulum is an eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells. Rough endoplasmic reticulums synthesize proteins, while smooth endoplasmic reticulums synthesize lipids and steroids, metabolize carbohydrates and steroids, and regulate calcium concentration, drug. The increased intracellular calcium gives a positive inotropic An inotrope (from Greek in-, meaning fibre or sinew) is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction effect. Digitalis also has a vagal effect on the parasympathetic nervous system The parasympathetic nervous system is a division of the autonomic nervous system (ANS), along with the sympathetic nervous system (SNS) and enteric nervous system (ENS or "bowels NS"). The ANS is a subdivision of the peripheral nervous system (PNS). ANS sends fibers to three tissues: cardiac muscle, smooth muscle, or glandular tissue, and as such is used in reentrant cardiac arrhythmias Cardiac dysrhythmia is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular and to slow the ventricular rate during atrial fibrillation Atrial fibrillation is the most common cardiac arrhythmia (abnormal heart rhythm) and involves the two upper chambers (atria) of the heart. Its name comes from the fibrillating (i.e. quivering) of the heart muscles of the atria, instead of a coordinated contraction. It can often be identified by taking a pulse and observing that the heartbeats don'. The dependence on the vagal effect means that digitalis is not effective when a patient has a high sympathetic nervous system The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's resources under stress; to induce the flight-or-fight response. It is, however, constantly active at a basal level in order to maintain homeostasis drive, which is the case with acutely ill persons, and also during exercise.

Digitalis toxicity (Digitalis intoxication) results from an overdose of digitalis and causes anorexia, nausea, vomiting and diarrhea, as well as sometimes resulting in xanthopsia (jaundiced or yellow vision) and the appearance of blurred outlines (halos). Bradycardia Bradycardia , as applied to adult medicine, is defined as a resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart. It sometimes results in fainting, 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 a rare example of a drug that is derived from a plant that was formerly used by folklorists Folkloristics is the formal academic study of folklore. The term derives from a nineteenth century German designation of folkloristik to distinguish between folklore as the content and folkloristics as its study, much as language is distinguished from linguistics. The adjective "folkloristic" for an academically oriented study is also and herbalists An herbalist is a professional trained in herbalism, the use of herbs to treat others. Professional herbal designations include the following:: herbalists have largely abandoned its use because of its narrow therapeutic index The therapeutic index , is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death. Quantitatively, it is the ratio given by the lethal dose divided by the therapeutic dose. A therapeutic index is the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective 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 person's pulse represents the tactile arterial palpation of the heartbeat. Sphygmology is a term from perhaps the 2nd century AD that roughly translates as "all that is known about the pulse". The pulse may be palpated in any place that allows an artery to be compressed against a bone, such as at the neck , at the wrist ( was understood, it was employed for a variety of purposes, including the treatment of epilepsy Epilepsy (from the Ancient Greek ἐπιληψία — "to seize") is a common chronic neurological disorder characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy, with almost 9 and other seizure disorders, which are now considered to be inappropriate treatments.

Toxicity

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

The entire plant is toxic (including the roots and seeds), although the leaves of the upper stem are particularly potent, with just a nibble being enough to potentially cause death. Early symptoms of ingestion include nausea Nausea , is a sensation of unease and discomfort in the upper stomach with an urge to vomit. An attack of nausea is known as a qualm, vomiting Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure. The feeling that one is about to vomit is called nausea, which usually precedes, but does not always lead to,, diarrhea Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and electrolyte imbalances. In 2009 diarrhea was estimated, abdominal pain, wild hallucinations, delirium Delirium is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior. It typically involves other cognitive deficits, changes in arousal (hyperactive, hypoactive, or mixed), perceptual deficits, altered sleep-wake cycle, and, and severe headache. Depending on the severity of the toxicosis the victim may later suffer irregular and slow pulse, tremors A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal cords, trunk, and legs. Most tremors occur in the hands. In some people, tremor is a symptom of another, various cerebral disturbances, especially of a visual nature (unusual colour visions with objects appearing yellowish to green, and blue halos around lights), convulsions, and deadly disturbances of the heart. For a case description, see the paper by Lacassie.^[11]

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

Digitalis poisoning can cause heart block and either bradycardia (lowered heart rate) or tachycardia (increased heart rate), depending on the dose and the condition of one's heart. It should however be noted, that electric cardioversion (to "shock" the heart) is generally not indicated in ventricular fibrillation in digitalis toxicity, as it can increase the dysrhythmia in digitalis toxicity^{[citation needed]}. Also, the classic drug of choice for VF (ventricular fibrillation) in emergency setting,^[12] amiodarone, can worsen the dysrhythmia caused by digitalis, therefore, the second-choice drug Lidocaine is more commonly used.^{[citation needed]}

Digoxigenin

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

See also

• List of plants poisonous to equines

Footnotes

1. ^ ^{a b} Olmstead, R. G., dePamphilis, C. W., Wolfe, A. D., Young, N. D., Elisons, W. J. & Reeves P. A. (2001). "Disintegration of the Scrophulariaceae". American Journal of Botany (American Journal of Botany, Vol. 88, No. 2) 88 (2): 348–361. doi:10.2307/2657024. PMID 11222255. http://www.amjbot.org/cgi/content/full/88/2/348.
2. ^ OED: "Digitalis"
3. ^ Digitalis at Dictionary.com]
4. ^ ^{a b} cite web|url=http://www.arkive.org/foxglove/digitalis-purpurea/range-and-habitat.html|title=Foxglove (Digitalis purpurea)|last=Anon|work=Arkive: images of life on Earth|publisher=Wildscreen|accessdate=6 May 2010}}
5. ^ Lankester, Mrs. (1866). Boswell J.T.. ed. English Botany, Or, Coloured Figures of British Plants (full text). VI campanulacae to verbanacea. Sowerby J, Smith C, Johnson J.E, Salter J.W. (III ed.). London: Edward hardwicke. pp. 128. http://books.google.com/?id=V0cAAAAAQAAJ&pg=PA128&dq=foxglove+finger+like&cd=3#v=onepage&q=foxglove%20finger%20like.
6. ^ Anon. "Foxglove: Digitalis purpurea (Scrophulariaceae)". Wildflowers in Bloom. Wildseed farms. http://aggie-horticulture.tamu.edu/wildseed/27/27.4.html. Retrieved 7 May 2010.
7. ^ Klein, Carol (18 May 2002). "How to grow: Foxgloves". The Telegraph (London, UK: Telegraph Media Group Limited). http://www.telegraph.co.uk/gardening/howtogrow/3300521/How-to-grow-Foxgloves.html. Retrieved 6 May 2010.
8. ^ Goldthorp WO (2009). "Medical Classics: An Account of the Foxglove and Some of its Medicinal Uses by William Withering, published 1785". Brit Med J 338: b2189.
9. ^ . In contemporary medicine, a purer form of digitalis (usually digoxin) is obtained from Digitalis lanata.
10. ^ Digoxin comes from Digitalis lanata. Hollman A. BMJ 1996;312:912. online version accessed 18 Oct 2006 [1]
11. ^ A non-fatal case of intoxication with foxglove, documented by means of liquid chromatography-electrospray-mass spectrometry. Lacassie E et al., J Forensic Sci. 2000 Sep;45(5):1154-8. Abstract accessed online 19 Sep 2006. [2]
12. ^ "European Resuscitation Council". http://www.erc.edu. ^{[verification needed]}

References

• Richard B. Silverman, The Organic Chemistry of Drug Design and Drug Action.
• Flora of Turkey. Edinburgh University Press.

External links

• Flora Europaea: Digitalis species list
• Molecule of the Month - Digitalis
• eMedicine link
• Grecian Foxglove USDA Noxious Weed List.
• Purple Foxglove USDA Noxious Weed List.

Categories: Antiarrhythmic agents | Medicinal plants | Plantaginaceae | Poisonous plants

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