Cardiac glycosides are naturally occurring compounds present in various plant species, known for their potent effects on the cardiovascular system. These compounds primarily act by inhibiting the sodium-potassium ATPase pump, which leads to an increase in intracellular calcium levels and subsequently enhances cardiac contractility. Although certain cardiac glycosides, such as digoxin, are used therapeutically under controlled conditions, their presence in some plants poses a significant risk of poisoning if ingested—whether accidentally or intentionally.

Several ornamental and wild plants contain cardiac glycosides, including Digitalis purpurea (foxglove), Nerium oleander (oleander), Thevetia peruviana (yellow oleander), and Convallaria majalis (lily of the valley). Ingestion of these plants can lead to serious and potentially fatal outcomes, including life-threatening cardiac arrhythmias, gastrointestinal disturbances, and neurological symptoms.

Historically, cardiac glycoside-containing plants were used medicinally by ancient Egyptian and Roman civilizations as emetics and for managing heart conditions. Recognition of their toxic properties dates back centuries and was notably documented in 1785, when William Withering published a landmark paper describing both the therapeutic and toxic effects of foxglove (Digitalis purpurea).

Despite modern advancements in medicine, cardiac glycoside toxicity from herbal sources continues to be a public health concern. For example, Digitalis lanata has been mistakenly used in place of plantain in herbal bowel-cleansing products, resulting in cases of poisoning. Furthermore, some Asian herbal remedies have been found to contain cardiac glycosides, contributing to additional reports of human toxicity.

Exposure to cardiac glycoside-containing plants is relatively uncommon. According to data from the 2022 American Association of Poison Control Centers (AAPCC), out of 47,956 reported single-plant exposures, approximately 2,007 were attributed to plants containing cardiac glycosides. This represents around 4% of all plant-related poisoning cases reported that year.

However, in certain regions, intentional ingestion of these plants is a more frequent and serious concern. In northern Sri Lanka, for example, the seeds of Thevetia peruviana commonly known as “lucky nuts” or yellow oleander are often used as a means of self-poisoning. Thousands of such cases are reported annually, and without treatment, the case fatality rate is estimated to range between 5% and 10%.

Inhibition of Na⁺/K⁺-ATPase

Cardiac glycosides bind to and inhibit the Na⁺/K⁺-ATPase pump, preventing the exchange of intracellular sodium for extracellular potassium.

As intracellular sodium levels rise, the sodium-calcium exchanger (NCX), which normally removes calcium in exchange for sodium, becomes less effective.

Increase in Intracellular Calcium

The impaired function of the NCX leads to accumulation of intracellular calcium within cardiac myocytes.

Elevated calcium enhances myocardial contractility (positive inotropy), which is beneficial in heart failure treatment but in toxic doses, this disrupts normal cardiac conduction and rhythm.

Electrophysiological Effects

Increased intracellular calcium and decreased potassium result in prolonged depolarization and increased automaticity, particularly in the atria and ventricles.

This predisposes to arrhythmias, such as premature ventricular contractions, atrioventricular (AV) block, atrial tachycardia, and life-threatening ventricular fibrillation.

Autonomic Nervous System Effects

Cardiac glycosides also increase vagal tone, slowing conduction through the AV node. This may lead to bradycardia and various degrees of heart block.

Human exposure to cardiac glycoside-containing plants can occur in various ways. The most common route is ingestion whether accidental or intentional of plant parts such as leaves, flowers, berries, seeds, or sap. Some individuals have also consumed herbal teas prepared from these plants. In more unusual cases, plant extracts have been deliberately administered via injection. Other anecdotal or folkloric exposure routes include drinking water from vases that held Convallaria majalis (lily of the valley), eating food stirred with toxic plant parts, or inhaling smoke from burning glycoside-containing vegetation.

Numerous plants are known to contain cardiac glycosides. Some of the most frequently encountered include:

Cerbera odollam and Cerbera manghas (commonly known as bintaro or “Indian suicide tree”)

Cheiranthus cheiri (wallflower)

Apocynum cannabinum (dogbane)

Strophanthus gratus (source of ouabain)

Urginea maritima and Urginea indica (squill)

Convallaria majalis (lily of the valley)

Thevetia peruviana (yellow oleander)

Nerium oleander (oleander)

Digitalis purpurea and Digitalis lanata (commonly known as foxglove)

Inadvertent ingestion of plants containing cardiac glycosides is rarely fatal. However, other toxic plants with similar cardiotoxic properties such as aconite have been associated with fatal poisonings. When death does occur from cardiac glycoside toxicity, it is typically due to life-threatening arrhythmias and severe, treatment-resistant hyperkalemia. Importantly, the severity of hyperkalemia serves as the most critical prognostic factor in these cases.

Age group:

Children: At risk from accidental ingestion of colorful plant parts.

Adolescents/Adults: More likely involved in intentional ingestion (e.g., self-harm).

Elderly: Risk from misusing herbal remedies or confusing them with medications.

General Appearance

May appear lethargic, confused, or diaphoretic

Signs of distress or agitation in severe poisoning

Vital Signs

Bradycardia (most common)

Hypotension may be present in severe cases

Cardiovascular

Irregular heart rhythm

Pulse deficit

Gastrointestinal

Nausea, vomiting, abdominal pain, and diarrhea

Dehydration signs if GI symptoms are severe

Neurological

Dizziness, confusion, weakness

In severe cases: seizures, syncope, or coma

Visual

Xanthopsia (yellow-tinted vision)

Blurred vision, visual halos, or scotomas (rare but characteristic)

Skin

Pallor or cool, clammy skin in circulatory compromise

Associated Comorbidity or Activity:

Psychiatric Disorders

Use of Herbal Remedies

Cognitive Impairment

Outdoor or Gardening Activities

Low Socioeconomic Status

Acuity of presentation:

Cardiac glycoside plant poisoning typically presents with acute onset of symptoms, often within 1 to 6 hours after ingestion, although the exact timing may vary depending on the plant species, amount consumed, and individual patient factors.

Initial Phase (Within Hours)

Symptoms may begin with gastrointestinal complaints such as nausea, vomiting, abdominal pain, and diarrhea.

These symptoms are due to direct irritation of the GI tract and early systemic effects of the toxin.

Cardiac Manifestations

As absorption progresses, the cardiac effects become more pronounced.

Patients may develop bradycardia, atrioventricular (AV) block, or ectopic beats early on.

Without intervention, this can escalate to ventricular tachycardia, ventricular fibrillation, or asystole, often due to increasing intracellular calcium and hyperkalemia.

Electrolyte Abnormalities

Hyperkalemia develops due to inhibition of the Na⁺/K⁺-ATPase pump, which leads to potassium leaking out of cells.

The degree of hyperkalemia is closely correlated with the severity of toxicity and is a strong predictor of mortality.

Neurological and Visual Symptoms

Patients may also report confusion, weakness, dizziness, and visual disturbances (e.g., blurred or yellow-tinted vision-xanthopsia), though these tend to appear after cardiac and GI symptoms.

Clinical Urgency

The presentation is considered acutely life-threatening and demands immediate emergency care.

Patients often require continuous cardiac monitoring, electrolyte correction, and potentially antidotal therapy (e.g., digoxin-specific antibody fragments).

Initial Stabilization

Assess and support airway, breathing, and circulation (ABCs)

Begin continuous cardiac monitoring

Establish IV access

Administer oxygen if hypoxic

Decontamination

Activated charcoal (single or multiple doses) if the patient presents within 1–2 hours of ingestion and airway is protected

Gastric lavage is rarely used-consider only in massive, recent ingestion under expert guidance

Antidotal Therapy

Digoxin-specific antibody fragments (Digibind/DigiFab):

Indicated for life-threatening arrhythmias, serum K⁺ >5.5 mmol/L, or severe poisoning

Dosage based on estimated ingestion or clinical severity

Electrolyte and Metabolic Correction

Hyperkalemia:

Treat with insulin + glucose, sodium bicarbonate, and beta-agonists

Avoid calcium (may worsen cardiac glycoside toxicity)

Magnesium sulfate:

Administer for arrhythmias, especially if torsades de pointes or suspected intracellular magnesium depletion

Correct hypokalemia cautiously if present

Arrhythmia Management

Atropine: for symptomatic bradycardia or AV block

Lidocaine or phenytoin: for ventricular arrhythmias

Avoid electrical cardioversion unless the patient is unstable, as it may worsen toxicity

Monitoring and Supportive Care

Admit to ICU or telemetry unit for close monitoring

Repeat electrolytes, renal function, and ECG

IV fluids to support blood pressure if hypotensive

Consider temporary pacing in refractory bradyarrhythmias

Emergency Medicine

Remove or Limit Access to Toxic Plants

Eliminate or avoid planting toxic species such as oleander, foxglove, yellow oleander, and lily of the valley in homes, schools, playgrounds, and elderly care facilities.

Replace high-risk plants with non-toxic alternatives in gardens and public spaces.

Safe Storage and Labeling

Keep herbal preparations and plant-based products clearly labeled and out of reach of children, especially in households using traditional medicine.

Avoid storing food near plant materials or using utensils that have contacted toxic plants.

Education and Awareness

Educate the public, especially parents, caregivers, gardeners, and teachers, about dangerous plants and their appearance.

Display warning signs in botanical gardens and community spaces where toxic plants are present.

Supervision of At-Risk Individuals

Monitor young children, individuals with cognitive impairment, and psychiatric conditions who may be prone to accidental or intentional ingestion.

Secure environments in mental health settings to prevent access to toxic plants for self-harm.

Safe Disposal of Plant Waste

Properly dispose of plant clippings, flowers, and seeds, especially from toxic species, to prevent accidental ingestion by children or pets.

Emergency Medicine

Activated charcoal

Activated charcoal is commonly used in emergency departments to manage poisonings caused by a wide range of drugs and chemicals. Its highly porous structure allows it to adsorb between 100 and 1000 mg of a substance per gram, depending on the specific compound. It is important to note that activated charcoal is insoluble in water.

For maximum effectiveness, it should be administered as soon as possible after ingestion of a toxic substance. In some cases, multiple doses may be beneficial to reduce systemic absorption and enhance elimination of certain toxins, particularly those undergoing enterohepatic or enteroenteric circulation.

Emergency Medicine

Sodium bicarbonate

Intravenous sodium bicarbonate, administered as an initial bolus followed by continuous infusion, has been used for its alkalinizing effects to maintain a serum pH between 7.5 and 7.55. In isolated case reports, this approach has been associated with improvement in hypotension and narrowing of a widened QRS complex.

Emergency Medicine

Magnesium sulfate

Magnesium sulfate possesses antidysrhythmic properties that can be beneficial in the management of digoxin toxicity. Although its precise mechanism of action remains uncertain, it is believed to suppress delayed afterdepolarizations, enhance Na⁺/K⁺-ATPase pump activity, and potentially counteract the effects of cardiac glycosides at the sarcolemmal Na⁺/K⁺-ATPase receptor site.

Magnesium also plays a vital role as a cofactor in numerous enzymatic reactions involved in neurotransmission and muscular excitability. Notably, intracellular magnesium deficiency may be present even when serum magnesium levels appear normal. As a result, magnesium supplementation can be a valuable therapeutic measure in managing digoxin-induced arrhythmias.

Emergency Medicine

Phases of management

Initial Stabilization (Resuscitation)

Airway, Breathing, Circulation (ABCs): Ensure airway patency, adequate oxygenation, and hemodynamic stability.

Cardiac Monitoring: Continuous ECG monitoring to detect dysrhythmias.

IV Access: Establish intravenous lines for fluid resuscitation and medication administration.

Baseline Labs: Serum electrolytes (especially potassium, magnesium), renal function, digoxin levels (if applicable), and arterial blood gas.

Decontamination

Activated Charcoal: Administer as early as possible if the patient presents within 1-2 hours of ingestion and airway is protected.

May be repeated in certain cases to interrupt enterohepatic circulation of cardiac glycosides.

Gastric Lavage: Rarely indicated and only considered if life-threatening ingestion occurred within the last hour.

Antidotal Therapy

Digoxin-specific antibody fragments (Digibind/DigiFab): Used in severe or life-threatening toxicity.

Indicated for life-threatening arrhythmias, significant hyperkalemia (>5.5 mEq/L), or ingestion of large amounts of plant material.

Supportive and Symptom-Specific Management

Arrhythmia Management:

Atropine for symptomatic bradycardia or heart block.

Lidocaine or phenytoin may be used for ventricular arrhythmias.

Avoid calcium in hyperkalemia associated with digoxin toxicity.

Electrolyte Correction:

Correct hypokalemia cautiously (if present).

Magnesium sulfate may be beneficial even if serum levels are normal.

Treat hyperkalemia with insulin-glucose, bicarbonate, and beta-agonists but avoid calcium if digoxin toxicity is suspected.

Monitoring and Disposition

Continuous cardiac monitoring until arrhythmias resolve.

Repeat labs to track electrolyte trends and renal function.

ICU admission may be required for severe toxicity.

Psychiatric evaluation in cases of intentional ingestion.