Common Foxglove

Plantaginaceae (Mare's-tail family)(Previously in Scrophulariaceae)

[IFBC-E-flora]

[E-flora]


Identification

"Digitalis purpurea is a BIENNIAL growing to 1.2 m (4ft) by 0.6 m (2ft in) at a medium rate.
It is not frost tender. It is in flower from Jun to September, and the seeds ripen from Aug to October. The flowers are hermaphrodite (have both male and female organs) and are pollinated by Bees.It is noted for attracting wildlife." [PFAF]
"Suitable for: light (sandy), medium (loamy) and heavy (clay) soils. Suitable pH: acid, neutral and basic (alkaline) soils. It can grow in semi-shade (light woodland) or no shade. It prefers dry or moist soil."[PFAF]

Synonyms

Origin Status: Exotic [E-flora]
General: Robust usually biennial herb from fibrous roots; stems erect, 0.5-1.5 m tall, unbranched, densely grey-hairy and becoming glandular upward. [IFBC-E-flora]
Leaves: Alternate, egg-shaped to lanceolate, 10-40 cm long, coarsely toothed, green and soft-hairy above, grey-woolly beneath, narrowed to the winged stalk, biggest and most numerous at the base in a rosette, reduced upward. [IFBC-E-flora]
Flowers: Inflorescence a long, narrow, leafy-bracted, 1-sided, terminal raceme of numerous stalked, nodding flowers, the stalks 5-20 mm long; corollas gaping-tubular, 4-6 cm long, weakly 2-lipped, shortly 5-lobed, the lower 3 lobes fused into the longer, more prominent of the 2 lips, pink-purple with deeper purple spots on inside of lower lip, the lips fringed with hairs, sparsely long-hairy in the throat; calyces deeply 5-lobed, the lobes somewhat leaflike, lance-egg-shaped, 1-1.8 cm long; stigmas 2-lobed; stamens 4. [IFBC-E-flora]
Fruits: Capsules, egg-shaped, about 12 mm long; seeds numerous, small, about 0.5 mm long. [IFBC-E-flora]
Characteristics: The plant is very poisonous; it tastes hotbitter with a slightly unpleasant odor.[PDR]
USDA Flower Colour: Purple
USDA Blooming Period: Summer
USDA Fruit/Seed characteristics:

Colour: Black
Present from Summer to Fall

[USDA-E-flora]


Habitat / Range
Moist to mesic roadsides, fields, clearings and forest edges in the lowland zone; common in SW BC, infrequent in the Queen Charlotte Islands; introduced from Europe. [IFBC-E-flora]
"Acid soils in woods, heaths, mountain grasslands etc[9, 17]. Western Europe, including Britain, from Norway to Spain and Sardinia." [PFAF]


Additional Notes
"Foxgloves are native to Europe but have escaped from gardens to become well established in coastal British Columbia, particularly along roadsides and in forest clearings. Although magenta-flowered foxgloves are most common, many populations, even small ones, are polymorphic for flower colour. Flowers may be dark magenta, light magenta, or white, and the spots on the flowers may be purplish or yellowish to light brown. The genetics of flower and spot colour were worked out in Britain soon after the science of genetics was discovered in 1900, and the results were published in 1910. Three different genes were involved. One, M, produces the magenta pigment, an anthocyanin, and results in magenta flowers with purple spots. The homozygous recessive, mm has white flowers with yellowish or brownish spots. Its flowers have no anthocyanin pigment. A separate dominant gene, D, darkens the pigment, resulting in dark magenta flowers. So plants with a dominant M allele, for pigment, are dark magenta if they also have a D allele and are light magenta if they are homozygous recessive (dd) for the D gene. The D allele therefore enhances the expression of the M allele. It has no effect on mm plants, which have no anthocyanin pigment in their flowers. In addition, a separate dominant white gene exists. A dominant W allele produces white flowers, even if the plant also has the M allele for magenta pigment. (The recessive allele does not have this effect). A plant that is homozygous mm is already white flowered, so the W allele has no effect in this case. A plant with a W allele is white flowered, so the D allele has no effect on a plant with a W allele. Although the W allele prevents the expression of M, the W allele does not effect the colour of the spots. Thus, a plant with the W allele and the M allele has white flowers with purple spots, and a plant with the W allele that is also homozygous mm has yellow to brownish spots, just like the wwmm plant, which produces no anthocyanin pigment anywhere on the flower."
Source: Extracted with permission from Griffiths and Ganders 1983, Wildflower Genetics: A Field Guide for British Columbia and the Pacific Northwest. [E-flora]


Hazards

All parts of the plant are highly poisonous[9, 10, 19, 65, 76, 222]. Unsafe for self-medication. Monitoring by a physician to determine correct dose recommended. For overdose give activated charcoal. Can be fatal especially to children [301]. [PFAF].

Precautions and Adverse Reactions
General: Because of the narrow therapeutic range of digitalis glycosides, a certain percentage of patients may experience side effects immediately upon administration of therapeutic dosages: hypertonia in gastrointestinal area, loss of appetite, vomiting, diarrhea and headache.
Drug Interactions: The simultaneous administration of arrhythmogenic substances (sympathomimetics, methylxanthines, phosphodiesterase inhibitors, quinidine) increases the risks of cardiac arrhythmias.[PDR]

Overdosage
With overdosage, in addition to the already-mentioned symptoms, the following can also occur: Heart: cardiac rhythm disorders, all the way up to lifethreatening ventricular tachycardia, atrial tachycardia with atrioventricular block Central nervous system: stupor, visual disorders, depression, confused states, hallucinations, psychoses Lethal dosages lead to heart failure or asphyxiation. Administration over extended periods leads in rare cases to gynecomastia. Because of the difficulties in standardizing the drug, the administration of pure glycosides is to be preferred (digitoxin). The first measures to be taken in case of poisoning are gastric lavage and activated charcoal instillation. All other measures proceed according to the symptoms. For loss of potassium, careful replenishment is necessary. For ectopic irritation build-up in the ventricle, administration of phenytoin as an antiarrhythmatic is recommended. Lidocaine should be used in cases of ventricular extrasystole, and for partial atrioventricular block, atropine is recommended. The prophylactic installation of a pacemaker is often necessary. For elimination of the glycosides hemoperfusion is possible, the administration of cholestyramine for interrrupting the enterohepatic circulation and/or the application of digitoxin antibodies (antigen-binding fragments, digitalis antidote {Boehringer Mannheim} , is very likely only fully effective with digitoxin poisoning).
The drugs and pure glycosides should be administered in the following situations (among others): atrioventricular block of the 2nd and 3rd degree, hypercalcaemia, hypocalcaemia, hypertrophic cardiomyopathy, carotid sinus syndrome, ventricular tachycardia, thoracic aortic aneurysm, WPW-syndrome.[PDR]

Once digitalis toxicity is diagnosed, digitalis and diuretic use should be discontinued.[PDBHM]


Other Uses

Medicinal Uses

Ethnobotanical Uses [DukePhyto]

Asthma Krochmal; Bactericide* Eb31: 35;
Cardiotonic** Woi.3, Al-Rawi, FontQuer, Krochmal, Steinmetz, Takeda;
Diuretic Steinmetz; Dropsy Woi.3; Edema Al-Rawi;
Fatality Lewis;

Fever Krochmal;
Heart Martinez, Woi.3;
Insanity Krochmal;
Neuralgia Krochmal;
Palpitation Krochmal; Poison Al-Rawi,
Steinmetz, Woi.3;

Renitis Woi.3;
Sedative Steinmetz;
Stimulant Steinmetz;
Stimulant(Cardio) Eb33: 189, Singh;
Tonic Eb33: 189, Singh, Steinmetz;
Tumor(Abdomen) Hartwell

Cardiac medicine


Various Other Uses
Digitalis purpurea, foxglove


History
1775: William Withering, a British physician with a strong interest in botany, introduces the drug digitalis (Foxglove Digitalis purpurea) into common medical practice for the treatment of dropsy. Dropsy is a now-obsolete term for edema (fluid retention or swelling) due to heart failure.[UXL]

Lore
".... But everywhere else, the association is with the fairies, as many of the local names for the plant confirm. It is Fairies’ glove, fingers, thimbles, hats, caps and dresses, and so on. When the plant bows its head, it is a sure sign that a fairy is passing (Boase). “Fairies have been seen dancing under foxgloves in Cusop Dingle within the memory of some now living there” (Leather). But of course they are seen to a much greater extent in Ireland – see Yeats (Irish fairy and folk tales) – “and away every one of the fairies scampered off as hard as they could, concealing themselves under the green leaves of the lusmore, where, if their little red caps should happen to peep out, they would only look like its crimson bells …”. Indeed, the Shefro, one of Ireland’s more gregarious fairies, is always described as wearing foxglove flowers (Wentz). (Lusmore, the great herb, is the name normally used for foxglove in Ireland).
As so often happens in folklore, the fairies’ favourite plant is also the one that offers most protection against them. In Ireland particularly, it can break the fairy spell (but can also cause the individual to be fairy struck (Wilde. 1902)). Nevertheless, it can cure any disease the fairies might cause (Logan). It is very useful when dealing with a changeling, a child “in the fairies”, as is sometimes said. The child is bathed in the juice, and fairy-struck children had to be given the juice of twelve (or some say ten) leaves of foxglove (Wilde. 1902). Or a piece of the plant could be put under the bed. If it is a changeling, the fairies would be compelled to restore the true child (Mooney). Simpler still, put some leaves on the child itself, and the result would be immediate (Gregory). And instructions from County Leintrim advised a suspicious parent to “take lusmore and squeeze the juice out. Give the child three drops on the tongue, and three in each ear. Then place it [the suspected changeling] at the door of the house on a shovel (on which it should be held by someone) and swing it out of the door on the shovel three times, saying “If you’re a fairy, away with you”. If it is indeed a fairy child it will die that night; but if not it will surely begin to mend” (Spence. 1949).
The Irish also used it as an effective charm against witchcraft. The patient was rubbed all over with it – a dangerous practice, and the patient may die of it, especially if tied naked to a stake, as was the custom once (Wilde. 1890).
.... The dried leaves are the source of a very potent drug that has the effect of reducing the frequency and force of the heart action, so it is given in special cases as a sedative, especially in heart disease. It was Dr William Withering (1741-1799), from Wellington, Shropshire, who first introduced digitalin into general medical practice. He published “an account of the Foxglove and some of its medical uses” in 1788. It is said he got his information from a witch. But this is indeed a dangerous plant, which animals always avoid. All parts are poisonous, but especially the seeds. The leaves are more active before than after flowering (Long. 1924). There was another use of the toxic principle; that was in what the Americans call a “chemical jury”. In other words it was used in ordeal trials to test guilt or innocence – if he survived he was innocent! (Thomson. 1976).
Gypsies use an ointment made from the fresh leaves to cure eczema (Vesey- Fitzgerald), and in early times the leaves were used mainly as an external application for wounds and ulcers in the legs (Clair), for the toxic potentialities were recognized very well early on. The gypsy usage for ulcers was certainly known very early, for in the Anglo-Saxon version of Dioscorides (in Cockayne’s translation) we have “For inflammatory sores, take leaves …, work to a poultice, lay to the sore”, and also “for a pimply body, take this same wort and fine flour, work to a poultice, lay it to the sore”. Much later, there are records from the Highlands for this use of the leaves on boils, and also on bruises (Grant), or to cure erysipelas (Polson. 1926), while on Skye a plaster made from them used to be applied to remove pains that follow fever (Martin).
Along with barley meal and some other herbs, it was included in an Irish preparation to treat epilepsy (Logan), but what herb was not tried at some time or other? As has been said (Thomson), desperate conditions demand desperate remedies! It must have been a quite dangerous practice, but there are other records of foxglove leaf infusions being taken. Gypsies use a very weak infusion of the dried leaves for fevers (Vesey-Fitzgerald), and foxglove tea was apparently a standard domestic remedy for dropsy (Beith). Irish people used to make a tincture for it with gin, and then use a very small quantity on loaf sugar (Egan). But given the known effect on the heart, there should be no surprise at that. But using the leaf infusion as an emetic, as was done in Ireland (Logan) is another matter. Other Irish uses, for lumbago (Ô’Súilleabháin), or for hydrophobia (Wood-Martin), for example, did not need internal consumption. But there is another case of an infusion taken internally; according to the Times Telescope, 1822, “the women of the poorer class in Derbyshire used to indulge in copious draughts of foxglove tea, as a cheap means of obtaining the pleasures of intoxication”. Actually the practice was far from being confined to Derbyshire.[DPL Watts]

Gender: Feminine
Planet: Venus
Element: Water
Powers: Protection
Magical Uses: Grown in the garden it protects it, as well as the home. In the past, housewives in Wales used the leaves of the foxglove to make a black dye, which they used to paint crossed lines on their cottage's stone floors. This was done to keep evil from entering the house.
Foxglove is poisonous; do not take internally.[EMH Cunningham]


Pharmacology

Activities (Digitalis)[HMH Duke]
  • Antidote (f; CRC);
  • Antitumor (1; CRC);
  • Cardiotonic (f; CRC);
  • Cordial(f; CRC);
  • Diuretic (f; CRC);
  • Myocardiocontractant (f; PH2);
  • Negative Chronotropic (f; PH2);
  • Poison (1; CRC);
  • Positive Inotropic (f; PH2);
  • Sedative (f; CRC);
  • Vasculostimulant (f; CRC).

Digitalis also acts as a diuretic. In Withering’s time, it became a popular treatment for dropsy (DROP-see), an old-fashioned term for EDEMA. People with edema often have swollen feet, ankles, and lower legs due to water buildup in their tissues. Fluid retention in the tissues of the body can be very dangerous. It is frequently related to congestive heart failure, which can be deadly. As of 2005, digitalis-type drugs were still being used in the treatment of heart failure. By strengthening the contractions of the heart muscle, digitalis helps pump excess fluids throughout the body. When the heart works more efficiently, fluids are less likely to pool, or accumulate, in the feet and legs.[UXL]

Digitalin
Standard granule—Gr. 1-67, gm. .001. [Shaller]
Active Principles. The so-called active medicinal principles consist of a number of glucosides: Digitalin, digitalein, digitonin, digitin and digitoxin. Unfortunately, great confusion exists regarding these preparations, which has been fostered by pharmacopoeial errors. Thus the digitalin of Homolle and Quevenne, recognized by French authority, is an amorphous, yellowishwhite powder, inodorous, intensely bitter to taste, extremely irritating to the nostrils, and highly poisonous; it is sometimes found as small scales. It is chemically a mixture of the digitalin of the German pharmacopoeia and the digitoxin of Schmiedeberg. Another form that has the sanction also of the French Codex is digitaline (mark the final e) cristallisee, or the digitalein of Nativelle, and appears as white, crystalline tufts or needles, and consists almost wholly of Schmiedeberg's digitoxin. It is very bitter to taste, slowly eliminated and consequently cumulative in action, and should be dispensed only when "crystallized digitalin" is ordered. Both the foregoing are insoluble in water or ether, but the crystallized form yields readily to chloroform and rectified spirit. [Shaller]

Digitalis should not be given simply because valvular lesions are present. There must be diminished blood-pressure and dilated arterioles, feeble cardiac action, retarded flow of blood which produces venous congestion, scanty secretion of urine, oedema and dyspnea. The heartaction must be enfeebled and rapid. If it is irregular or intermittent it is no contraindication, only that it beat frequently or feebly.
Digitalis is a much abused remedy. It is a powerful vasoconstrictor and an inhibitor of the heart-action, and because it is given in cases which neither require an inhibitory action of the heart nor a contraction of the arterioles, it necessarily does harm, perhaps produces death, and the remedy is credited with being uncertain in its action.
A good strong pulse, with normal amount of urine excreted, contraindicates its use, and if it were given where such conditions exist the pulse would beat slower and harder and the quantity of urine would be diminished. Digitalis should be confined to the treatment of enfeebled conditions of the heart and blood-veins with disturbed circulation of the blood. Digitalis is a diuretic only when the arterial capillaries are so dilated as to lessen the blood-pressure in the malpighian bodies so that the water cannot be forced through them. It is hardly probable that digitalis can have diuretic effects without first increasing blood-pressure. [Shaller]

Digitalis may sometimes cause sudden death in such cases and is not therefore a safe remedy to give in large doses frequently repeated to such patients. Caution should always be used. Strychnine is preferable and is freer from danger, and one need not fear that one's patient may die suddenly and rather unexpectedly as is often the case when digitalis is given.. [Shaller]

CUMULATIVE ACTION
There is no doubt that sudden deaths occur more frequently while digitalis is being administered than from any other medicine. As some one has said, because this remedy is used to treat diseases of the heart where sudden deaths are frequent, nothing much is thought of these sudden deaths, and the remedy, least of all, suspected. Yet, the fact remains that digitalis is the direct cause.
It may be difficult to satisfactorily explain how death occurs. Repeated doses of medicines are not absorbed into the blood, accumulating without producing any effect. Then after several days, all of this accumulated medicine does suddenly let loose all of its energy, as by explosion, causing death; just as if all the medicine which had been given for days in divided doses should have been given at one dose and quickly absorbed. The probabilities are, that it is a matter of cumulative doses.
All medicines as soon as they enter the body also begin to leave it. It is very well known that many medicines may be detected in the urine within five minutes after their administration. Also when single doses of some medicines are given, their presence can be demonstrated in the urine for several days thereafter. While there may be some decomposition of some of the alkaloids or other active principles, yet, whether taken in their pure isolated state as digitalin, or if the digitalis leaves are taken, the result is the same, the kidneys eliminate the alkaloids or glucosides. The digestive system, by its chemistry and solvent powers separates the active medicinal principles and other matters from the insoluble.
The most powerful of the active principles of digitalis is digitoxin. It is more slowly eliminated from the blood than are the others. The prolonged action of digitalis depends altogether upon the slowness with which its active principles are eliminated by the kidneys. When poisoning does occur from frequently-repeated doses, the kidneys have not had sufficient time to remove the medicine from the blood. There is therefore an accumulation in the blood, which may increase to such an extent as to finally cause death. It is simply over-dosing, caused by giving the medicine too frequently without allowing time for its elimination. There are many physicians who only give two doses of digitalis daily. This is probably the correct method to prevent accumulation of the active principles in the blood when large doses are given. The frequent repetition of small doses of digitalin, as is customary with those who practise dosimetry, does not seem to be accompanied by the same danger as when cruder preparations are given. Possibly digitalin is not as potent as digitalis. The latter may contain more of the poison, digitoxin.
One point should not be lost sight of during a course of digitalis treatment:
If a patient is sick enough to be treated with digitalis, particularly if the patient is aged or the pulse very feeble, he is sick enough to be in bed and kept there in a persistent recumbent position until digitalis has accomplished its work. Why? Because such patients are particularly benefited by the recumbent position. It of itself will lower the rapidity of the heart-action by fifteen or more beats.
The action of digitalis should be more carefully watched than that of opiates because it will kill quicker. In such cases, everything seems to be going along nicely, when the patient rises from his bed and falls over dead. Died of heart disease? No. Died of digitalis poisoning. This is likely to be so in treating typhoid fever of pneumonia with digitalis.
There may be two ways of explaining such results. Digitalis has probably reduced the pulsations below the normal. The heart contracts with extraordinary vigor. On suddenly assuming the erect position more force is needed and the heart must beat with more vigor and, being in a state of tonic activity, its systolic action is so great that it remains in the condition of tonic contraction or systole, and the patient dies.
On the other hand, when too much digitalis has been taken, it loses its stimulating action and becomes. a paralyzant; when extra effort is made as by standing, the arterioles dilate from weight of blood, the heartaction becomes very rapid and embarrassed and, because of the gravitation of blood to the extremities, the brain centers become anemic and fatal syncope results.
It took Koppe four days to recover from the effects of a single dose of 1- 33 gr. digitalin.
Give digitalis to feeble patients while in bed until the heart beats normally and the secretion of urine is increased. This will require five or six days.
Then stop giving the drug, but still keep the patient in bed for several days and keep him on 1-30 gr. doses of strychnine every four hours. It is never safe to give digitalis when the number of heart-beats is normal, and surely not when it is below normal. In those cases where in the recumbent or sitting position the number of pulsations is normal, but in which on standing or upon slight exertion it increases thirty or more beats, digitalis must be very cautiously used. Strychnine, apocynin and cactin are better remedies and are free from danger.
In the treatment of post-partum hemorrhage, digitalis has frequently been used with success. As it acts chiefly through the vasomotor constrictions in reducing the caliber of the arterial capillaries by causing contraction of the involuntary muscular fibers, its beneficial effects can be readily explained. In hemorrhages of all kinds, where feeble heart-action and diminished bloodpressure are prominent, digitalis is indicated. Dose dram ij of the infusion or two to four granules of digitalin every two hours for three doses, after which the remedy must be stopped. Digitalis is also highly recommended in the treatment of spermatorrhea. Similar conditions which guide its use in other diseases also answer here, viz., relaxation of the vascular system, evidenced by enlarged veins, easily induced sexual excitement with its accompanying congestion. The greater the extent of self-abuse, the more frequent the indulgence in sexual intercourse, particularly to excess, the more readily is venous congestion of the genital apparatus produced. In such cases the most insignificant and trivial thought or act produces an erection. This does not represent sexual vigor, but sexual weakness. The genital vasomotor centers are congested and become extremely sensitive to the slightest irritation. Excessive irritation causes loss of their muscular toning property which gives way to relaxation. This relaxed condition of the genital organs calls for the use of digitalis. The general circulatory system, in fact the entire body, is relaxed and toneless. Improve the circulation by digitalis and small doses of strychnine. Overcome the extreme sensitiveness and the exaggerated irritability of the vasomotor and genital centers by cicutine. If "nervousness" is marked it is best to begin treatment with cicutine until emissions are controlled, then follow it with strychnine and digitalis. Remember always that when the pulse is restored to the normal number of beats, digitalis should be withdrawn and strychnine given in its stead.
Digitalis is a remedy of greatest therapeutic value. It is the most important medicine used in the treatment of heart-diseases, particularly when accompanied by dropsy. No other remedy can approach it in regard to usefulness. All other heart remedies are compared with it, and the highest attribute that can be applied to any aspirant for honor in the treatment of cardiac diseases is to say it has a "digitalis-like action." It frequently, however, brings disappointment. This is chiefly because it is not given in relaxed conditions of the heart and blood-vessels. It no doubt varies considerably in its composition, depending upon the soil, atmospheric condition, seasons and general environment, and upon the freshness of the plant employed.
There are few drugs toward which individual members of the human family are so generally and differently idiosyncratic. Again, the actions of watery and alcoholic preparations are by no means identical, owing to the differences in the solubility of the various glucosides in these menstrua; an infusion, for instance, holds in solution chiefly the digitonin, while the tincture contains digitalin and digitalein, neither contains much digitoxin, but the tincture necessarily carries more than the infusion. Notably the infusion is more directly and promptly diuretic, and the B.P. tincture more so than that of the U. S. P., but the latter two afford the best results when the heart alone is to be acted upon. But it is doubtful if the tincture alone ever acts as a true diuretic, except in the presence of a heart-lesion, such as is found in connection with some form of hydrops. The drug often fails completely in securing the desired action clinically, because the wrong preparation is employed.—(Sajous' Annual).
Digitalis occupies an almost isolated and rather unfortunate position, because the isolated principles do not constantly represent the medicinal activity of the whole plant. It is a very important medicine, and unlike most important remedial plants it refuses to yield up a reliable active principle. Four active medicinal principles have been isolated, not one of which fully represents the medicinal virtues of the leaf itself.
Ergot which has a similar action, i. e., vasoconstrictor, has nothing better to fully represent its medicinal properties than concentrated extracts. Aconitine, atropine, quinine, morphine, hyoscyamine, strychnine and colchicine, represent the. medicinal properties of the vegetable substances from which they are derived. They are reliable and can be given with the belief and the assurance that certain known results will follow their internal administration. This cannot be as strongly and as truly said of any of the products of digitalis. Digitalin has at times disappointed the writer more than any other active principle, inasmuch as it has failed to produce such positive, marked and constant results as the infusion. This is to be regretted exceedingly because of the important position that digitalis occupies.
The time will unquestionably come when the active medicinal principles of digitalis shall be uniformly produced, which does not seem to be so at the present time. Possibly, some one may hit upon the happy and correct combination of some of the four active principles as they exist in the plant. It is too late in the history of dosimetry to go into the advantages of the use of active principles over that of crude drugs. But until each one is satisfied in his own mind that the isolated substance placed in his hands can do as much and more than the plant itself, he is justified in refusing to use it. As long as the physician feels sure that the crude drug is superior to the active principles found in the market, that it produces better results, he should use the crude drug. He should use whatever produces the best results in his hands, irrespective of what others may believe.
The writer confines the use of digitalis almost exclusively to those conditions in which there is weakening of the muscular structure of the entire circulatory system, blood-vessels as well as heart, manifested by relaxation of blood-vessels, venous stasis, oedema, and scanty urine. Digitalis or digitalin has no place in the treatment of febrile diseases except in combination with aconitine and strychnine, simply because the heart beats rapidly. Cactin, strychnine and caffeine are better remedies to simply sustain the heart-action when it is needed in such cases. Apocynin has found great favor in the treatment of heart-diseases, in which digitalis is usually prescribed. It is greatly to be preferred to digitalin. In its action in reducing oedema and the number of heart-beats, as well as regulating irregularities, it is equal to digitalis, if not even more reliable. Besides it is a stomachic and is free from so-called cumulative effects.
Notwithstanding what has been said, if the symptoms are not urgent, digitalin is given a trial for five days. If no results manifest themselves within that time, apocynin or infusion of, digitalis is given. If no benefit accrues, caffeine and strychnine are added to the above remedies. If oedema is marked and the urine is still scanty, only a few ounces in twenty-four hours, calomel gr. 3 three times a day for three days is, given, guarded with codeine if necessary. If these fail, strophanthus or diuretin is given. If there is no improvement by this time the case is probably hopeless. Still, various combinations should be tried. The bowels should be freely moved and sometimes when all efforts seem to fail, relief will sometimes come.
Medicines that utterly fail in the beginning of treatment sometimes produce beneficial results when tried at another period. Various combinations can be made. Keep on trying, and do not give up a remedy until it has been pushed to produce its physiologic effect. If you stop short of this, the remedy has not received full justice, and cannot therefore be condemned.[Shaller]

Physiological Action Digitalis in full doses produces a great rise in arterial pressure, followed by a marked fall. It acts on the inhibitory nerves and on the heart muscle; the increased action being due to vasomotor spasm and to stimulation of the heart itself. A poisonous dose causes depression and a dicrotic pulse, while the immediate effect of moderate doses is to stimulate the heart. Its prolonged use weakens the heart muscle by decreasing its normal nutrition.
When given in frequent small doses, where absorption is immediate, it influences all of the organic functions as a depressant; it produces irritation of the stomach and bowels, increased action of the kidneys, and a marked change in the character, regularity and frequency of the pulse beat. The influence upon the heart is not always uniform in all such cases, but variable and often unreliable. The influence is marked and more immediate if a large dose is given and repeated a few times. The gastric and intestinal irritation is greatly increased, there is purging, violent vomiting, great prostration with dicrotic or tumultous, irregular, erratic and uncertain heart action.
In its general irritating influence upon organic function it may cause so marked an impression upon the renal circulation as to result in spasm of the vessel walls and suspension of renal action-suppression of urine with profound albuminuria.
Therapy—Digitalis is the direct heart stimulant. Its influence is sure and plainly apparent in marked sthenic conditions. In prostration or profound weakness, in sudden failure from violent injury, from '''surgical shock or from acute poisoning''', or in the crisis of extreme exhausting or protracted disease, its influence given in conjunction with general stimulants is decisive and satisfactory.
The agent sustains the action of the heart, but does not impart tone as cactus does, by increased nerve force and improved nutrition of the organ. Its sustaining power can be maintained by proper administration until other measures supply deficient power, by encouraging reaction, or by general improved nutrition.
The influence of digitalis in its stimulant effect is nearly diametrically opposed to that of aconite. In therapeutic action the two agents occupy the opposite extremes. For this reason digitalis, within the limits of its stimulant action, is a physiological antidote to aconite.
Digitalis slows a rapid and feeble pulse in asthenic fever. It is a sedative in fevers under those circumstances in which aconite is contraindicated. In prolonged cases where asthenic conditions prevail, and where the temperature remains high, with rapid, feeble, easily compressed pulse or irregular heart action, all the evidences of failure of vital force, digitalis is the fever remedy. It controls the pulse, reduces the temperature somewhat, and im. proves the heart action. Aconite, veratrum and the synthetic antipyretics will all increase the condition under such circumstances and are contraindicated.
In pneumonia, when the disease processes have had full sway, and the heart is unable to properly fill the pulmonary capillaries, and is depressed by the influence of the general disorder, and the general effects of the accumulated carbonic acid within the blood, and is labored and overtaxed and apparently slowly failing, this agent is directly useful. It promptly strengthens the heart and the nervous structure of the pulmonary apparatus at the same time.
In minute doses in children, if it be given with belladonna or other heart stimulants, it shows a most desirable influence in this class of cases, but should be stopped as soon as these results are obtained, that no untoward symptoms may occur.
Digitalis is a remedy for passive congestion where the blood stasis has occurred from feebleness and failure of the circulatory organs. It exercises a stimulating influence upon the entire apparatus; through its power of increasing heart action it imparts renewed force and an improved capillary tonus in every part. It such cases its influence resembles that of belladonna, although not so marked nor permanent.
Digitalis is a remedy for passive congestion where the blood stasis has occurred from feebleness and failure of the circulatory organs. It exercises a stimulating influence upon the entire apparatus; through its power of increasing heart action it imparts renewed force and an improved capillary tonus in every part. It such cases its influence resembles that of belladonna, although not so marked nor permanent.
In valvular diseases of the heart, with muscular relaxation and feebleness, it is a good remedy, but not always the best. It sustains the power for a time in those cases where there is stenosis, and where compensatory dilatation has previously occurred. In feeble, irregular and intermittent heart it is frequently prescribed with excellent results.
Digitalis is not found in the urine and does not directly influence the secretory or the excretory functions of the kidneys. Its apparent influence upon these organs is. due to the improved blood pressure from its direct influence upon the heart, inducing increased heart action. '''Renal congestion''' is overcome because the increased heart impulse drives the blood through the renal capillaries with renewed vigor, and there is thus a copious flow of the urine from improved renal circulation. Under these circumstances only, is it a valuable remedy in dropsy. In cardiac dropsy it acts most promptly if given in infusion in small and frequently repeated doses. Close watch must be kept for cumulative action. In dropsy from post-scarlatinal nephritis, a dram or two of the leaves in a pint of water is thoroughly steeped. Of this from a teaspoonful to a tablespoonful may be given every two or three hours.
In general dropsy from heart disease there is deficient capillary circulation, especially when lying down; the pulse is irregular, intermittent and feeble, the urine is small in quantity, with a large percentage of albumen. Its power over the heart influences this entire train of symptoms directly. Patients taking digitalis in full doses for an immediate effect should remain in the recumbent position. This position greatly favors its sedative and tonic action, and patients have died upon being raised to a sitting posture immediately after taking an extreme dose of this agent. Syncope, especially in children, is common at such a time. The profound influence of the remedy prevents the occurrence of the natural change in the action of the heart, from a prone position to the sitting posture. Digitalis may exercise no apparent influence upon the system when proper doses are given regularly for some days, until suddenly violent poisonous effects may appear, with irregular and greatly depressed heart action, vertigo, extreme wakefulness, vomiting, irritation of the bowels, with pain and sometimes violent purging.
The cause or manner of its accumulation is variously explained and is not well understood. Several theories are advanced, none of which are satisfactory. No other heart remedy has these objections. Cumulative action often shows itself first by the influence of the agent upon the kidneys, in suspending or restraining their action. Consequently if desirable results from the use of this agent do not appear, and there is a decrease in the quantity of urine passed, the agent should be suspended, at least for a time.[Ellingwood]


Toxicokinetics

The cardiac glycosides of D. purpurea are hydrolyzed to digitoxin, gitoxin, and gitalin with only small amounts of digoxin formed from hepatic metabolism. Hence, D. purpurea toxicity may be prolonged because of the long serum half - life of digitoxin (4 – 5 days). Digitoxin undergoes metabolism to digitoxigenin, digitoxigenin mono-digitoxoside, and gitoxin. Additionally, the kidneys excrete some digitoxin unchanged. Liquid chromatography/electrospray/mass spectrometry (LC/ES/MS) analysis of samples from a patient during the first 5 days after the ingestion of foxglove tea demonstrated digitoxin, digitoxigenin, gitoxin, and digitoxigenin mono-digitoxoside in the serum and gitaloxin, digitoxin, digitoxigenin, gitoxin, and digitoxigenin mono digitoxoside in the urine.[9] Digitoxin was the digitalis glycoside present in the highest concentration (112.6 ng/ mL) in the serum 8 hours after the ingestion. Relatively high serum concentrations of gitaloxin appeared only on the fifth day, when the serum gitaloxin concentration (112.6 ng/mL) exceeded the serum concentrations of all other cardiac glycosides.[TNS]

Toxicodynamics/Kinetics Upper limit of peak toxicity: 12 hours; all symptomatic patients should be observed for a minimum of 24 hours.[PTH]

Adverse Reactions Cardiovascular: Sinus bradycardia
Signs and Symptoms of Overdose GI effects (nausea and vomiting) usually precede cardiovascular effects by several hours. Asystole, AV block, bradycardia, decreased QT interval and prolonged P-R interval, fibrillation (atrial), flutter (atrial), heart block (first, second, and third degree), hypotension, ventricular arrhythmias. Contact dermatitis, delirium, dizziness, confusion, fatigue, headache, hyperkalemia and seeing yellow halos have also been reported.[PTH]


Phytochemicals

It has been reported that digitalis essentially contains three important primary glycosides namely: Purpurea glycoside A, Purpurea glycoside B, and Purpurea glycoside C, which upon hydrolysis give rise to digitoxin, gitoxin and gitalin respectively. These secondary glcosides on further hydrolysis yields noncarbohydrate moieties (called aglycones or genins) digitoxigenin, gitoxigenin and gitaligenin or gitaloxigenin respectively. The series of all these hydrolysed products and their structures are summarised below.
Besides, the crude drug also contains a good number of other glycosides (e.g.; digitalin, diginin); saponins (e.g.; digitonin, gitin and digitosaponin); tannins, gallic, formic, acetic, succinic and benzoic acids; fatty acids and enzyme digipuridase solely responsible for hydrolysis of purpurea glycosides.[PCPB]

The cardioactive glycoside content of D. purpurea leaf is 0.15–0.4%, consisting of about 30 different structures. The major components are based on the aglycones digitoxigenin, gitoxigenin, and gitaloxigenin (Figure 5.103), the latter being a formate ester. The glycosides comprise two series of compounds, those with a tetrasaccharide glucose–(digitoxose) 3– unit and those with a trisaccharide (digitoxose)3– unit. The latter group (the secondary glycosides) is produced by partial hydrolysis from the former group (the primary glycosides) during drying by the enzymic action of a β-glucosidase which removes the terminal glucose. Thus, the principal glycosides in the fresh leaves, namely purpureaglycoside A and purpureaglycoside B (Figure 5.103), are partially converted into digitoxin and gitoxin respectively (Figure 5.103), which normally predominate in the dried leaf. These transformations are indicated schematically in Figure 5.104. In the fresh leaf, purpureaglycoside A can constitute about 50% of the glycoside mixture, whilst in the dried leaf the amounts could be negligible if the plant material is old or poorly stored. The gitaloxigenin-based glycosides are relatively unstable, and the formyl group on the aglycone is readily lost by hydrolysis. Other minor glycosides are present, but neither the fresh nor dried leaf contains any significant quantities of the free aglycones.[MNP Dewick]

  • 1-METHOXY-2-HYDROXY-3-METHYL-ANTHRAQUINONE - Leaf - DUKE1992A
  • 1-METHOXY-2-METHYL-ANTHRAQUINONE - Leaf - DUKE1992A
  • 14ALPHA-DIGIPRONIN - Plant - DUKE1992A
  • 16-ACETYLGITOXIN - Leaf - DUKE1992A
  • 3-METHOXY-2-METHYL-ANTHRAQUINONE - Leaf - DUKE1992A
  • 3-METHYL-ALIZARIN - Leaf - DUKE1992A
  • 3-METHYLPURPURIN - Plant - DUKE1992A
  • 4-HYDROXYDIGITOLUTEIN - Leaf - DUKE1992A
  • 6,8-DIHYDROXYMYRICETIN - Leaf - DUKE1992A
  • ACETIC-ACID - Leaf DUKE1992A
  • ACETYL-CHOLINE - Leaf DUKE1992A
  • APIGENIN - Flower DUKE1992A
  • APIGENIN-GLUCOSYLAPIOSIDE - Flower - DUKE1992A
  • BENZOIC-ACID - Leaf - DUKE1992A
  • CAFFEIC-ACID - Leaf - DUKE1992A
  • CARDEONOLIDES Leaf 1600 4000 DUKE1992A
  • CEROTIC-ACID Leaf DUKE1992A
  • CHLOROGENIC-ACID Leaf DUKE1992A
  • CHOLINE Leaf DUKE1992A
  • CITRIC-ACID Leaf DUKE1992A
  • CYANIDIN-3,5-DIGLUCOSIDE Leaf DUKE1992A
  • DEGALACTOTIGOGENIN Leaf DUKE1992A
  • DESGLUCODIGITONIN Seed 2500 DUKE1992A
  • DIGACETENIN Leaf DUKE1992A
  • DIGALOGENIN Leaf DUKE1992A
  • DIGALONIN Leaf DUKE1992A
  • DIGICITRIN Leaf DUKE1992A
    DIGIFOLEIN Leaf DUKE1992A
    DIGIFUCOCELLOBIOSIDE Seed 30 DUKE1992A
    DIGININ Leaf DUKE1992A
    DIGIPRONIN Leaf DUKE1992A
    DIGIPROSIDE Leaf 5 HHB
    DIGIPURPURIN Leaf 225 560 DUKE1992A
    DIGIPURPUROGENIN Plant DUKE1992A
    DIGITALIN Plant DUKE1992A
    DIGITALONIN Leaf DUKE1992A
    DIGITOGENIN Leaf DUKE1992A
    DIGITOLUTEIN Leaf DUKE1992A
    DIGITONIN Leaf DUKE1992A
    DIGITONIN Seed 4000 DUKE1992A
    DIGITOPURPON Leaf DUKE1992A
    DIGITOXIGENIN Leaf 1 10 DUKE1992A DIGITOXIGENIN-BISDIGITOXOSIDE Leaf 10 30 DUKE1992A
    DIGITOXIGENIN-GLUCOMETHYLOSIDE Leaf 30 100 DUKE1992A
    DIGITOXIN Leaf 20 3000 DUKE1992A
    DINATIN Leaf DUKE1992A
    EVATROMONOSIDE Leaf 5 50 DUKE1992A
    F-GITONIN Leaf DUKE1992A
    FAT Leaf 12200 DUKE1992A
    FAT Seed 500000 DUKE1992A
    FERULIC-ACID Leaf DUKE1992A
    FORMIC-ACID Leaf DUKE1992A
    GALLIC-ACID Leaf DUKE1992A
    GITALIN Leaf 3000 9000 DUKE1992A
    GITALOXIGENIN Leaf 1 10 DUKE1992A
    GITALOXIGENIN-BISDIGITOXOSIDE Leaf 1 20 DUKE1992A
    GITALOXIN Leaf 10 300 DUKE1992A
    GITOGENIN Leaf 2000 3000 DUKE1992A
    GITONIN Leaf DUKE1992A
    GITONIN Seed 1500 DUKE1992A
    GITORIN Plant DUKE1992A
    GITOROSIDE Leaf 5 30 DUKE1992A
    GITOSTIN Seed 200 DUKE1992A
    GITOXIGENIN Leaf 1 10 DUKE1992A
    GITOXIGENIN-BISDIGITOXOSIDE Leaf 1 20 DUKE1992A
    GITOXIN Leaf 20 250 DUKE1992A
    GITOXINCELLOBIOSIDE Seed 2 DUKE1992A
    GITOXOSIDE Plant DUKE1992A
GLUCO-EVATROMONOSIDE Leaf 20 250 DUKE1992A
GLUCO-EVATROMONOSIDE Seed 200 DUKE1992A
GLUCODIGIFUCOSIDE Leaf 10 30 DUKE1992A
GLUCODIGIFUCOSIDE Seed 600 DUKE1992A
GLUCODIGITOXIGENIN-BISDIGITOXOSIDE Leaf 20 120 DUKE1992A
GLUCODIGITOXIGENIN-BISDIGITOXOSIDE Seed 10 DUKE1992A
GLUCODIGITOXIGENIN-GLUCOMETHYLOSIDE Leaf DUKE1992A
GLUCOGITALOXIGENIN-BISDIGITOXOSIDE Leaf 10 100 DUKE1992A
GLUCOGITALOXIGENIN-BISDIGITOXOSIDE Seed 20 DUKE1992A
GLUCOGITALOXIN Leaf 100 1000 DUKE1992A
GLUCOGITALOXIN Seed 200 DUKE1992A
GLUCOGITOROSIDE Leaf 20 150 DUKE1992A
GLUCOGITOROSIDE Seed 30 DUKE1992A
GLUCOGITOXIGENIN-BISDIGITOXOSIDE Leaf 20 80 DUKE1992A
GLUCOLANADOXIN Leaf 20 200 DUKE1992A
GLUCOLANADOXIN Seed 150 DUKE1992A
GLUCOVERODOXIN Leaf 100 400 DUKE1992A
GLUCOVERODOXIN Seed 1000 DUKE1992A
INOSITOL Leaf DUKE1992A
ISOCHRYSOPHANOL Leaf DUKE1992A
LACTIC-ACID Leaf DUKE1992A
LANADOXIN Leaf 5 30 DUKE1992A
LANAFOLIN Leaf DUKE1992A
LOLIOLIDE Leaf DUKE1992A
LUTEOLIN Leaf DUKE1992A
LUTEOLIN-5-XYLOSIDE-7-GLUCURONIDE Leaf DUKE1992A
LUTEOLIN-7-D-GLUCOSIDE Leaf DUKE1992A
LUTEOLIN-7-XYLOSIDE-5-GLUCURONIDE Leaf DUKE1992A
LUTEOLIN-DIGLUCOSIDE Flower DUKE1992A
LUTEOLIN-L-7-GLUCOSYL-GLUCURONIDE Leaf DUKE1992A
LUTEOLIN-L-7-GLUCURONIDE Leaf DUKE1992A
MELISSYL-ALCOHOL Leaf DUKE1992A
NEODIGITOGENIN Plant DUKE1992A
NEODIGTALOGENIN Plant DUKE1992A
NEOGITOSTIN Seed 200 DUKE1992A
ODOROBIOSIDE-G Leaf 20 50 DUKE1992A
ODOROBIOSIDE-G Seed 50 100 DUKE1992A
ODOROBIOSIDE-H Leaf 5 DUKE1992A
P-COUMARIC-ACID Leaf DUKE1992A
PELARGONIDIN-3,5-DIGLUCOSIDE Leaf DUKE1992A
PHOMARIN Leaf DUKE1992A
PHOMARIN-6-METHYL-ETHER Leaf DUKE1992A
PURLANOSIDE-B Seed 20 DUKE1992A
PURPNIN Plant DUKE1992A
PURPRIN Leaf DUKE1992A
PURPRONIN Leaf DUKE1992A
PURPUREAGITOSIDE Plant DUKE1992A
PURPUREAGLYCOSIDE-A Leaf 200 1200 DUKE1992A
PURPUREAGLYCOSIDE-A Seed 30 DUKE1992A
PURPUREAGLYCOSIDE-B Leaf 200 800 DUKE1992A
PURPUREAGLYCOSIDE-B Seed 10 DUKE1992A
SAPONINS Seed 10000 DUKE1992A
SITOSTEROL Leaf DUKE1992A
SPIROSTANOL-GLYCOSIDES Leaf 10000 DUKE1992A
STROSPESIDE Leaf 50 200 HHB
SUCCINIC-ACID Leaf DUKE1992A
TIGOGENIN Leaf 4000 7000 DUKE1992A
TIGONIN Leaf DUKE1992A
TIGONIN Seed 300 DUKE1992A
TRIACONTANE Leaf DUKE1992A
VERODOXIN Leaf 50 200 HHB
[DukePhyto]

Cultivation

"Easily grown in ordinary garden soil, especially if it is rich in organic matter[1]. Prefers a light dry soil in semi-shade[17] but succeeds in full sun if the soil is moist[200]. Grows well in acid soils[17]. Plants are hardy to about -25oc[187]. The foxglove is a very ornamental plant that is easily naturalized in the semi-shade of a woodland[1]. It contains glycosides and forms the basis of an important heart medicine for which it is cultivated commercially[4]. This species is commonly used by herbalists, whereas D. lanata is more commonly grown for supplying the pharmaceutical industry[238]. The plant contains much greater concentrations of the medically active ingredients when it is grown in a sunny position[115]. The flowers are very attractive to bees[4, 24]. Individual plants can produce up to 2 million seeds[4]. Members of this genus are rarely if ever troubled by browsing deer or rabbits[233]. A good companion plant, it stimulates the growth of nearby plants, growing well with pine trees[18, 20, 54]. Special Features:Attractive foliage, Not North American native, Naturalizing, All or parts of this plant are poisonous, Suitable for cut flowers." [PFAF]

Propagation
Seed - surface sow early spring in a cold frame. The seed usually germinates in 2 - 4 weeks at 20oc[175]. When they are large enough to handle, prick the seedlings out into individual pots and plant them out in the summer. If you have sufficient seed it can be sown outdoors in situ in the spring or autumn." [PFAF]


References

  1. [Duke] Accessed Feb 10, 2015, http://www.ars-grin.gov/duke/
  2. [E-flora] http://linnet.geog.ubc.ca/Atlas/Atlas.aspx?sciname=Digitalis%20purpurea Accessed Dec 9, 2014
  3. [PFAF] Accessed Feb 10, 2015, http://www.pfaf.org/user/Plant.aspx?LatinName=Digitalis+purpurea
  4. [Shaller]A Therapeutic guide to Alkaloidal-Dosimetric-Medication, John M. Shaller, M.D., 2nd ed. The clinic publishing co., Boston, 1907
  5. [UXL] U.X.L Encyclopedia of Drugs & Addictive Substances, V.5 Opium to ranquilizers, Barbara C. Bigelow, MAT, 2006 Thompson Gale, Farmington Hills, MI

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