Foxglove (Digitalis purpurea L.): A Comprehensive Reference
1. Identity, Botanical Classification, and Natural Source
Foxglove, known scientifically as Digitalis purpurea L., is a toxic species of flowering plant in the plantain family Plantaginaceae, native to and widespread throughout most of temperate Europe. It has also naturalized in parts of North America, as well as some other temperate regions.
The name Digitalis is derived from the Latin for finger (digitus), which represents the form of the tubular flowers, somewhat shaped like fingers. The German name Fingerhut (thimble) suggested to Leonhard Fuchs, the well-known German herbalist of the sixteenth century, the employment of the Latin adjective Digitalis (from Digitabulum, a thimble) as a designation for the plant, which, as he remarked, up to the time when he thus named it, in 1542, had had no name in either Greek or Latin.
The generic name Digitalis was given to this species and its close relatives by the famous Swedish naturalist Carl Linnaeus in his 1753 publication Species Plantarum.
The genus was traditionally placed in the figwort family, Scrophulariaceae, but phylogenetic research led taxonomists to move it to the Veronicaceae in 2001. More recent phylogenetic work has placed it in the much enlarged family Plantaginaceae.
Digitalis purpurea is an herbaceous biennial or short-lived perennial plant. The leaves are spirally arranged, simple, 10–35 cm (3.9–13.8 in) long and 5–12 cm (2–5 in) broad, and are covered with gray-white pubescent and glandular hairs, imparting a woolly texture.
Digitalis purpurea grows in acidic soils, in partial sunlight to deep shade, in a range of habitats, including open woods, woodland clearings, moorland and heath margins, sea-cliffs, rocky mountain slopes and hedge banks.
Common Names and Synonyms
Common foxglove, Digitalis purpurea, is an herbaceous biennial or short-lived perennial from western Europe in the plantain family (Plantaginaceae) that grows in woodland clearings, mountainsides and especially on disturbed sites, as well as being used as a garden ornamental. This species is sometimes called purple foxglove, fairy gloves, fairy bells, or lady's glove. Other historical folk names include Witches' Gloves, Dead Men's Bells, Bloody Fingers, Virgin's Glove, Fairy Caps, and Throatwort.
Related Species of Pharmaceutical Importance
In contemporary medicine, digitalis (usually digoxin) is obtained from D. lanata. The most commonly used cardiac glycosides, digoxin and digitoxin, are derived from foxgloves, respectively Digitalis lanata and Digitalis purpurea. Digitoxin is another derivative that has remained in clinical use in countries outside the US, such as Canada and Europe.
Common Forms and Preparations
The part used medicinally is the leaf. Historically, preparations have included decoctions (boiled leaf tea), powdered dried leaves, and leaf extracts. Withering gathered dried leaves at the time of flowering, which were boiled in water, the resulting medicine being administered to patients. After 1776, Withering gradually used foxglove more in the form of powdered leaves, which produced fewer side effects such as nausea, vomiting, and diarrhea.
Digoxin continues to be derived from the foxglove plant through a modern manufacturing process, which involves extracting digitalis from dried foxglove leaves to produce pure digoxin for pharmaceutical applications. Digitoxin is isolated by extraction of the leaves and seeds of Digitalis purpurea L. (purple foxglove) with 50% ethanol and subsequent treatment with the enzyme digilanidase, which effects cleavage of the β-D-glucose moiety at the chain end of the main glycoside, purpureaglycoside A.
2. Traditional and Historical Uses
Pre-Withering Period: Medieval Europe and Celtic Traditions
Original therapeutic usage of Digitalis sp., commonly known as foxglove, can be found dating back to tenth century England, Wales, and Europe where it was used as an expectorant and treatment for epilepsy, swelling, and sore throats. Officially entering the London Pharmacopoeia in the mid 1600s, and subsequently the pharmacopoeia of most other countries by the eighteenth century, the late 1700s saw the emergence of Digitalis as a remedy for "dropsy."
Six plants could be hypothetically attributed to the Celtic (Welsh) herbal tradition, including foxglove (Digitalis purpurea L.); this provides initial evidence for traces of a Celtic framework in the Welsh herbal tradition. Foxglove was mentioned in the writings of Welsh physicians in 1250.
During the Middle Ages, foxglove (Digitalis spp.) has been considered to have multifarious healing properties, and the first reports of its role as an agent in the congestive heart failure treatment date from the year 1250.
In his De historia stirpium commentarii, published in 1542, Fuchs described the plant as a purgative and an emetic. Herbalists employed it to treat epilepsy, inflammation, and even tuberculosis (TB). Once the usefulness of digitalis in regulating the human pulse was understood, it was employed for a variety of purposes, including the treatment of epilepsy and other seizure disorders, which are now considered to be inappropriate treatments.
The English used foxgloves for many medicinal ailments including coughs, epilepsy and swollen glands. Welsh and Irish healers certainly incorporated foxglove into their remedies.
Under the Doctrine of Signatures — a pre-scientific European herbal tradition — foxglove flowers were supposed to look like an animal's open mouth; within the doctrine of signatures, this meant it must have some medicinal value in treatment of injuries of the mouth and throat. The speckles in the mouth of the flower were, according to the doctrine, symbolic of inflammation of the throat.
William Withering and the Codification of Digitalis Medicine (1775–1785)
In 1785, the British physician William Withering (1741–1799) published An account of the foxglove and some of its medical uses; with practical remarks on the dropsy, and some other diseases (Birmingham: Swinney). As the story goes, Withering knew of a healer who successfully treated cases of dropsy by administering an herbal tea to her patients. He went on to identify the plants that were used to prepare the tea and discovered later that the major active ingredient was Digitalis. Thanks to its cardio-tonic action, Foxglove was increasing cardiac activity and, as a consequence, drained the body.
Withering deduced that digitalis was the active ingredient in the formulation, and over the next ten years he carefully tried out different preparations of various parts of the plant (collected at different seasons), documenting 156 cases in which he had used digitalis, and describing the effects and the best — and safest — ways of using it.
Though foxglove had been used in folk medicine for centuries, Withering drew upon 156 of his own cases to objectively demonstrate its efficacy in treating dropsy, the edematous bodily swelling that typically accompanied heart failure. In particular, he noted that foxglove leaf preparations were efficacious in small, nontoxic doses and that their action varied according to the plant's stage of bloom.
Single case reports were the most widespread way of publishing original observations in Withering's time, but although he had collected records of nineteen cases of "dropsy" treated with digitalis before 1779, he decided not to report on the treatment until he had assembled all the 156 cases seen in his private practice, and seven whom he had treated at the Birmingham Hospital.
The use of D. purpurea extract containing cardiac glycosides for the treatment of heart conditions was first described in the English-speaking medical literature by William Withering, in 1785, which is considered the beginning of modern therapeutics.
Twentieth Century: Wartime Cultivation and Isolation of Pure Glycosides
Drugs were in short supply in Britain during World War II, leading to a governmental Vegetable Drugs Committee being set up. A coalition of medical experts and botanists worked with members of the public, including Women's Institutes, Boy Scouts and Girl Guides, who were encouraged to gather, grow and harvest foxglove.
Digoxin was first isolated from Digitalis purpurea leaves in 1930 by Dr Sydney Smith. Modern-day herbalists have largely abandoned the use of digitalis because of its narrow therapeutic index and the difficulty of determining the amount of active drug in herbal preparations.
3. Key Constituents and Active Compounds
Cardiac Glycosides (Cardenolides)
Leaves of wild varieties that have been used for medicinal purposes contain at least 30 different glycosides in total quantities ranging from 0.1% to 0.6%; these consist primarily of purpurea glycoside A (yielding digitoxin) and glycoside B, the precursor of gitoxin.
Digitalis purpurea is the source of the cardiac glycosides digitoxin, gitoxin, and gitalin. Common digitalis glycosides include digitoxin, gitoxin, and digoxin, derived from the aglycones digitoxigenin, gitoxigenin, and digoxigenin, respectively, linked to sugars such as digitoxose.
Digitoxin is derived from the leaves of D. purpurea, and digoxin is derived (after a mild alkaline hydrolysis step) from those of D. lanata, as are lanatoside C and deslanoside.
The content and the ratio of cardenolides in Digitalis species are regulated by the activity of enzymes responsible for the conversion of primary glycosides such as lanatoside A, lanatoside B, and lanatoside C into corresponding secondary glycosides digitoxin, gitoxin, and digoxin, respectively.
The steroid nucleus common to all cardiac glycosides contains an α,β-unsaturated lactone ring attached at the C-17 position. Without the sugar moieties, the steroid and unsaturated lactone part of the molecule is called a genin or an aglycone. The genins are usually less potent and have more transient actions due to altered pharmacokinetics than do the parent glycosides.
Structure–activity studies on the cardiac glycosides have demonstrated that the sugar moiety aids in bioavailability and solubility, whereas functionalization of the steroid nucleus with hydroxyl, methyl, and lactone ring groups is essential for pharmacological activity. The unsubstituted aglycone, or steroidal portion, is less active than the glycoside (sugar attached).
Other Phytochemical Constituents
The plant contains cardiac glycosides (including digoxin, digitoxin and lanatosides). Additionally, phenylethyl glycosides including purpureaside A, phenylpropanoid glucose esters, benzoquinolethanoid glucosides such as cornoside, furostane-type steroidal saponins, and disaccharides such as sucrose have been isolated from aerial parts of Digitalis species.
Biosynthetic pathways in the production of cardenolides are reliant on the enzymes of malonyltransferase and progesterone 5-beta-reductase.
Cardiac glycosides, e.g., digitalis and digoxin, are naturally occurring compounds found in various plants and amphibians, characterized by a steroid ring, a lactone ring, and a sugar moiety.
Pharmacokinetic Differences Between the Two Main Glycosides
The only structural difference between digoxin and digitoxin is a single hydroxyl group, which is missing in digitoxin. This small structural difference nevertheless results in major differences in pharmacokinetic properties of the two drugs. Approximately 70% of digoxin is excreted by the kidneys, which is directly proportional to the patient's glomerular filtration rate. Digitoxin rapidly strengthens the heartbeat but is excreted very slowly.
4. Mechanisms of Action
Inhibition of Na⁺/K⁺-ATPase (Sodium-Potassium Pump)
There is a large amount of evidence that the mechanisms of action of cardiac glycosides are mediated directly or indirectly by inhibition of the sodium/potassium pump enzyme, Na/K-ATPase.
Digitalis compounds are potent inhibitors of cellular Na⁺/K⁺-ATPase. This ion transport system moves sodium ions out of the cell and brings potassium ions into the cell. By inhibiting the Na⁺/K⁺-ATPase, cardiac glycosides such as digoxin cause intracellular sodium concentration to increase. This leads to an accumulation of intracellular calcium via the Na⁺-Ca²⁺ exchanger. In the heart, increased intracellular calcium causes more calcium to be taken up and subsequently released by the sarcoplasmic reticulum, thereby making more calcium available to bind to troponin-C, which increases contractility (inotropy).
Compelling direct evidence supporting cardiac glycoside–induced increases in intracellular Na⁺ concentration has now been obtained, and the mechanism of digitalis-induced positive inotropy is known to involve an altered balance between intracellular Na⁺ and Ca²⁺. The transmembrane Na⁺ influx occurring with each action potential, in the presence of diminished outward Na⁺ pumping due to digitalis, leads to an increase in intracellular Na⁺ concentration that in turn increases intracellular Ca²⁺ stores, either through enhanced Ca²⁺ entry, reduced Ca²⁺ efflux, or both, effects that are thought to be mediated via Na⁺-Ca²⁺ exchange.
Hemodynamic and Cardiac Effects
In treating heart failure, the cardiac glycosides of Digitalis function by increasing the strength and efficiency of ventricular contraction, thus shortening the length of contraction and allowing the heart muscle a longer relaxation time between contractions. This results in recovery of the myocardium, decreased heart rate, and improved renal function through enhanced circulation.
Digitalis is used to increase cardiac contractility (it is a positive inotrope) and as an antiarrhythmic agent to control the heart rate, particularly in the irregular (and often fast) atrial fibrillation.
Despite widespread acceptance into medical practice over more than 200 years, both the efficacy and the safety of this class of drugs continue to be a topic of debate. Moreover, despite the fact that the molecular target for the cardiac glycosides, the α-subunit of sarcolemmal Na⁺K⁺-ATPase (or sodium pump) found on most eukaryotic cell membranes, has been known for several decades, it remains controversial whether the sympatholytic or positive inotropic effects of these agents is the mechanism most relevant to relief of heart failure symptoms in humans with systolic ventricular dysfunction.
Vagomimetic Effects
Digoxin exerts vagomimetic effects, increasing parasympathetic tone and slowing conduction through the sinoatrial and AV nodes, resulting in negative chronotropy and rate control.
5. Body Systems and Health Areas of Association
- Cardiovascular system: Heart failure (systolic dysfunction), atrial fibrillation, atrial flutter, rate control
- Renal system: Historically used as a diuretic to reduce fluid retention in dropsy (edema)
- Central nervous system: Historical (now discredited) use in epilepsy; CNS toxicity is a recognized adverse effect
- Oncology (investigational): Emerging preclinical evidence for anticancer properties
6. Scientific Evidence by Area of Use
6.1 Heart Failure
The DIG Trial, a randomized, double-blind, placebo-controlled trial in over 7,000 patients with heart failure, showed a neutral effect on the primary study endpoint of mortality from any cause during an average follow-up of approximately 3 years.
The Digitalis Investigation Group (DIG) trial is the only large randomized clinical trial evaluating the efficacy of digoxin in patients with heart failure, as evidenced by a recent Cochrane Review; it reported a neutral effect on mortality and a significant reduction in heart failure hospitalizations.
Initial clinical trials of digoxin comparing the drug to vasodilators, milrinone, and placebo and the subsequent digoxin withdrawal trials showed substantial evidence that digoxin offered symptomatic benefits to patients with heart failure, but mortality benefits of digoxin remain controversial.
A post hoc analysis of the DIG study showed that patients who had higher serum digoxin concentrations had an absolute 11.8% increase in all-cause mortality.
The PROVED trial was a placebo-controlled, twelve-week duration study. It included patients with decreased systolic function, sinus rhythm, and stable heart failure symptoms who were using digoxin and diuretics. Patients from whom digoxin was removed presented with twice the worsening heart failure, reduction of exercise capacity, and also a reduction of left ventricular ejection fraction, compared to patients who kept digoxin therapy.
The RADIANCE study followed a similar protocol; however, the patients used ACE inhibitors besides digoxin and diuretics. The digoxin removal was associated with a six-fold worsening of heart failure, despite the maintenance of ACE inhibitors and diuretics. There was a worsening in functional capacity, quality of life, and ejection fraction in the digoxin removal group.
Digoxin increases left ventricular ejection fraction and alleviates symptomatic heart failure as evidenced by drug-related improvement in exercise capacity and reductions in heart failure–associated hospitalization and emergency room visits.
A prespecified subgroup analysis of patients enrolled in the DIG Trial with evidence of severe heart failure (as manifested by left ventricular ejection fraction less than 25%, or cardiothoracic ratio greater than 0.55) showed the benefit of digoxin. The following reductions in the combined endpoint of all-cause mortality or hospitalization were seen on digoxin compared with placebo: 16% reduction (95% CI, 7% to 24%) in patients with a left ventricular ejection fraction of less than 25%, and a 15% reduction (95% CI, 6% to 23%) in patients with a CTR greater than 0.55. Reductions in the risk of the combined endpoint of heart failure–related mortality or hospitalization were even more striking: 39% (95% CI, 29% to 47%) for patients with LVEF less than 25%, and 35% (95% CI, 25% to 43%) for patients with a CTR greater than 0.55.
Summary of evidence: The evidence for digoxin in heart failure is substantial but complex. While the DIG trial demonstrated clear reductions in heart failure hospitalizations and symptomatic benefit, no overall mortality benefit was demonstrated. Subgroup analyses suggest greater benefit in more severely ill patients. Evidence strength: high for symptomatic benefit; neutral for mortality.
6.2 Atrial Fibrillation and Atrial Flutter
A systematic review with meta-analysis and trial sequential analysis found 28 trials (n = 2,223 participants) evaluating digoxin for atrial fibrillation or atrial flutter. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions, the review found no evidence of a difference on all-cause mortality, serious adverse events, quality of life, heart failure, or stroke.
The analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo, with a mean difference of −12.0 beats per minute.
During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure.
Summary of evidence: Digoxin demonstrates clear short-term heart rate–lowering effects in atrial fibrillation. Evidence on long-term mortality outcomes is conflicting, with observational evidence suggesting possible harm and randomized evidence insufficient to confirm or refute this. Evidence strength: strong for acute ventricular rate control; unclear and contested for long-term mortality outcomes.
6.3 Anticancer Activity (Investigational)
In the context of cancer, a considerable number of in vitro and in vivo studies since the 1960s discuss a potential therapeutic benefit of digitalis glycosides on neoplastic cells due to antiproliferative effects by targeting various pathways. The discussion was initiated by the sporadic observation of reduced malignancies in patients treated with digitalis.
A growing body of evidence indicates that digitoxin cardiac glycoside is a promising anticancer agent when used at therapeutic concentrations. Digitoxin has a prolonged half-life and a well-established clinical profile. However, the anticancer mechanism of digitoxin or synthetic analogs is still subject to study, while concerns about digitoxin's cardiotoxicity preclude its clinical application in cancer therapeutics.
Cardiac glycosides are good candidates as drug leads in the treatment of cancer because of their structural diversities and potent biological activities. In one study, fifteen cardiac glycosides were isolated from Digitalis lanata Ehrh. Their structures were elucidated by HRESIMS and NMR spectroscopic methods. The cytotoxic activities of these glycosides were evaluated against three human cancer cell lines (A549, HeLa, and MCF-7 cell lines), and all of them showed strong activities at nanomolar scale.
The primary mechanism of action of these anticancer agents is by suppressing the Na⁺/K⁺-ATPase by decreasing the intracellular K⁺ and increasing Na⁺ and Ca²⁺. Additionally, cardiac glycosides were known to act as inhibitors of IL-8 production, DNA topoisomerase I and II, anoikis prevention, and suppression of several target genes responsible for the inhibition of cancer cell proliferation.
Digitalis compounds are phytoestrogens and bind to the estrogen receptor (ER), albeit with a lower affinity than estrogen itself. A large study enrolling more than 100,000 women revealed that current (but not former) digoxin use increased the relative risk of developing breast cancer.
Cardiac glycosides have a long history in treating heart diseases, but recent studies on cancer cell lines and animal systems have demonstrated anticancer and antiviral activities of several cardiac glycosides. Depending on these findings, cardiac glycosides have been identified as potential anticancer and antiviral agents that should be assessed in clinical studies.
Summary of evidence: Evidence for anticancer activity is largely preclinical — derived from cell line studies and animal models. No robust randomized clinical trials have evaluated cardiac glycosides as anticancer agents. The cardiotoxicity profile at effective concentrations remains a major barrier. Evidence strength: preliminary; in vitro and animal data only; no clinical evidence to date.
6.4 Edema / Dropsy (Historical and Contemporary)
Initially, digitalis was used to treat dropsy, which is an old term for edema. Subsequent investigations found that digitalis was most useful for edema that was caused by a weakened heart (i.e., heart failure).
One lasting contribution to medicine since its discovery in the 18th century has been the beneficial effect of the leaves of foxglove (Digitalis purpurea) in "dropsy," probably congestive heart failure in modern terms.
7. Dosage Forms and Reported Dosages
Digitalis leaf has a narrow therapeutic index, requiring close medical supervision for safe use. Traditional dosage starts at 1.5 g of leaf divided into 2 daily doses. Purified digoxin is typically used at daily doses of 0.125 to 0.25 mg.
Digoxin has a narrow therapeutic index, with recommended serum levels ranging from 0.8 to 2 ng/mL. Blood should be drawn at least 6 to 8 hours after the last dose to accurately measure serum digoxin levels. Toxicity risk increases as serum levels exceed 2.0 ng/mL.
Digoxin, a drug that is inexpensive and can be given once daily, represents the only orally available drug with positive inotropic effects approved for the management of heart failure.
Digoxin, a widely prescribed cardiac glycoside, is listed as an essential medicine by the World Health Organization and is one of the most prescribed naturally derived pharmaceutical products.
8. Safety Considerations, Toxicology, and Drug Interactions
General Toxicity
All parts of the plant are toxic, containing cardiac glycosides such as digitoxin and digitalin, and it is thought that the ingestion of two to three dried leaves could represent a fatal dose. Symptoms of poisoning include nausea, vomiting (sometimes persistent for more than 24 hours), abdominal pain, diarrhoea, headache and bradycardia. In severe cases, trembling, convulsions, delirium and hallucinations have been reported.
Cardiac symptoms caused by glycosides of Digitalis purpurea include strong cardiac contractions, prolonged diastole, pulse and cardiac rhythm abnormalities, hyperkalemia, and ventricular tachycardia. This may culminate in cardiac arrhythmias and asystole (cardiac arrest). Additionally, they cause myocarditis, myocardial lesions and hemorrhage. Digoxin overdose induces ECG changes, such as ST-depression, T-wave inversion, PR-interval prolongation and QT-interval decrease, thereby leading to the signs of cardiac toxicity.
Narrow Therapeutic Index
Because it has a narrow therapeutic index and multiple interactions, digoxin frequently causes toxicity with a wide range of symptoms and cardiac arrhythmias. Elevated serum digoxin levels have been linked to a higher risk of death in patients with heart failure or atrial fibrillation, even without signs or symptoms of toxicity.
Digoxin's narrow therapeutic window makes it susceptible to toxicity, necessitating careful dosing based on patient-specific factors, including renal function and drug interactions. Its proper dosing requires the clinician to be mindful of various patient characteristics, including age, gender, kidney function, and concomitant use of other drugs, to avoid potentially life-threatening toxicity.
Risk Factors for Toxicity
The toxicity risk increases with renal impairment, electrolyte abnormalities, and advanced age. Digoxin has several drug interactions; therefore, monitoring serum levels and electrolytes is crucial.
Adverse effects are concentration-dependent, and are rare when plasma digoxin concentration is less than 0.8 µg/L. They are also more common in patients with low potassium levels (hypokalemia), since digoxin normally competes with K⁺ ions for the same binding site on the Na⁺/K⁺ ATPase pump.
Common Adverse Effects
Common adverse effects (≥1% of patients) include loss of appetite, nausea, vomiting, and diarrhea as gastrointestinal motility increases. Other common effects are blurred vision, visual disturbances (yellow-green halos and problems with color perception), confusion, drowsiness, dizziness, insomnia, nightmares, agitation, and depression.
Digoxin toxicity is common, especially in patients with impaired kidney function, polypharmacy, or electrolyte derangements. Digoxin toxicity can present with a wide range of nonspecific gastrointestinal and central nervous system symptoms and several cardiac arrhythmias.
Drug Interactions
Many commonly used drugs interact with digoxin. The Class IA antiarrhythmic quinidine competes with digoxin for binding sites and depresses renal clearance of digoxin. These effects increase digoxin levels and can produce toxicity. Similar interactions occur with calcium-channel blockers and non-steroidal anti-inflammatory drugs. Other drugs that interact with digoxin are amiodarone (Class III antiarrhythmic) and beta-blockers. Diuretics can indirectly interact with digoxin because of their potential for decreasing plasma potassium levels (i.e., producing hypokalemia).
Beta-blockers and calcium channel blockers can potentiate digoxin's effects on AV node conduction, increasing the risk of bradycardia and advanced or complete heart block.
Management of Toxicity
Treatment of digoxin toxicity includes supportive management and digoxin-specific antibody fragments that can be used if the patient has life-threatening cardiac arrhythmias or electrolyte abnormalities. Treatment for digitalis poisoning is usually symptomatic and involves multi-dose activated charcoal and atropine.
Contamination of Dietary Supplements
The identification of lanatosides A and C by liquid chromatography and mass spectrometry in botanical dietary supplement products — particularly lanatoside C, for which there is no corresponding primary glycoside occurring in D. purpurea — confirms that contamination by D. lanata is identifiable and has occurred in commercial botanical products. On enzymatic hydrolysis and mild alkaline hydrolysis, lanatoside A yields digitoxin and lanatoside C yields digoxin. This has been documented as a source of inadvertent digitalis toxicity in supplement users.
Contraindications
Cardiac glycosides are contraindicated in ventricular fibrillations. An overdose of digoxin can lead to severe arrhythmias and malignant hyperkalemia. Digoxin may improve the quality of life in CHF patients, but it does not confer a mortality benefit, and its narrow therapeutic index limits its utility. Digoxin toxicity can present acutely, by an intentional or accidental overdose, or chronically, such as when patients on digoxin develop an acute kidney injury.
References
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