What Is Digoxin Toxicity?

Introduction

Digoxin, derived from foxgloves, is a medication used to manage chronic heart failure and irregular heart rhythms like atrial fibrillation and atrial flutter. It plays a pivotal role when conventional treatments prove insufficient. 

By modifying potassium and calcium levels, digoxin enhances heart muscle contraction and improves blood circulation. However, excessive digoxin levels can lead to toxicity, causing serious health issues. 

This article delves into the causes, risk factors, symptoms, and treatment of digoxin toxicity shedding light on its impact and ways to prevent its occurrence.

What is digoxin? 

Digoxin belongs to a class of medications called cardiac glycosides. It is a drug derived from the plant Digitalis purpurea, more commonly known as the foxglove. It is used to manage and treat chronic heart failure and irregular heart rhythms such as atrial fibrillation and atrial flutter.¹ It is normally recommended when first-line treatments are not enough to control the symptoms. 

Digoxin works by affecting the levels of certain minerals in the body, like potassium and calcium. These minerals play a crucial role in how your heart contracts. In addition, it helps increase the amount of calcium inside the heart cells. This increased calcium makes the heart muscle contract more strongly, helping the heart pump blood more effectively, so the heart does not need to pump blood to the rest of the body as frequently.² The rise of calcium levels caused by digoxin can impact the electrical signals that control the rhythm of heartbeats. The increased levels of calcium can reduce the electrical conduction in the heart, thereby decreasing the heart rate. 

Causes and risk factors

In England, approximately 3 million prescriptions are produced for digoxin and around 1% of patients will develop toxicity - a risk that increases with age.³ Those diagnosed with heart failure are normally given a medicine called a diuretic alongside digoxin. Diuretics remove excess fluid in the body and, as a result, cause a reduction in potassium levels. Low levels of potassium (hypokalemia) are the most common trigger of digoxin toxicity.⁴

A decline in kidney function can also lead to digoxin toxicity.⁴ Kidneys play a vital role in removing medication, including digoxin, from the body. When kidney function decreases, the ability to clear digoxin from the bloodstream is compromised. This results in high levels of digoxin accumulating in the body, increasing the risk of toxicity. 

Other risk factors that can lead to digoxin toxicity include:

• Hypothyroidism/hyperthyroidism (change in thyroid function)
• Ageing  
• Having had a heart attack
• Alkalosis - excess alkali (bases) in the body
• Acidosis - excess acid in the body
• Hypoxemia - low levels of oxygen in the blood

Additionally, there are medicines that are associated with digoxin toxicity. These include:

• Diuretics (e.g. bumetanide and furosemide)
• Anti-arrhythmic (e.g. amiodarone and verapamil)
• Beta-blockers (e.g. bisoprolol and atenolol)
• Benzodiazepines (e.g. diazepam)
• Calcium channel blockers (e.g. amlodipine and verapamil)
• Macrolide antibiotics (e.g. erythromycin and clarithromycin) 

It is important to inform your doctor or pharmacist about all medications that you take; this includes both prescription and non-prescription (over-the-counter) medications.

Symptoms of digoxin toxicity

Symptoms of digoxin toxicity are often non-specific, so you should be referred for further testing: 

• Visual disturbances (e.g. blurred vision, seeing spots, colour disturbances)
• Confusion 
• Gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea and abdominal pain)
• Faster heart rate
• Fatigue and weakness⁶

Symptoms associated with digoxin toxicity can develop within 1-2 hours of a sudden overdose.⁶ It can take more than twelve hours for the cardiac side effects to fully develop; as a result, it has been reported that irregular heart rhythms (cardiac arrhythmias) account for the majority of deaths.⁷ However, some may develop no symptoms of arrhythmia. 

Treatment of digoxin toxicity

There are evidence-based guidelines for the management of mild to moderate toxicity, resulting in a wide variety of treatment options available.⁸ However, severe toxicity needs to be treated in the hospital. 

Digoxin-specific antibody fragments, also known as Fab fragments, will be required for treatment.⁹ Fab fragments bind to the digoxin in the bloodstream, removing the excess digoxin and reducing its toxic effects on the body. Even though digoxin concentration does not necessarily correlate with symptoms of toxicity, it can be used to calculate the amount of the antidote required. However, this treatment can significantly reduce the level of potassium in the body, so potassium levels need to be monitored. Activated charcoal can be used as a treatment within two hours; however, support is required for such treatment.⁹  

A 12-lead echocardiogram (ECG) needs to be performed and closely monitored - an ECG can detect issues with the heart rate and rhythm. In addition, oxygen and electrolyte levels are monitored during digoxin poisoning treatment.

Prevention

Due to the small concentration range of digoxin that is effective in treating irregular heartbeats and chronic heart failure without causing toxicity (i.e. a narrow therapeutic window), consistent monitoring is vital. Seven days after starting digoxin, digoxin levels are measured, as this is when a steady level of digoxin is reached. Routine monitoring is not recommended once reaching therapeutic stability as there is no evidence from clinical trials to suggest that routine monitoring leads to better outcomes.¹⁰ 

According to the National Institute for Health and Care Excellence (NICE), digoxin levels are usually monitored after any dose changes, suspected signs and symptoms of toxicity or changes to medications taken alongside digoxin. In addition, people who have poor kidney function, electrolyte imbalances or suspected overdoses should be monitored for kidney function. Regular kidney function monitoring is important as the kidney is needed for the removal of digoxin. Regular kidney function tests such as serum creatinine and estimated glomerular filtration test (eGFR) help ensure that the kidneys are functioning correctly. This would help prevent the accumulation of digoxin and prevent any potential toxicity. 

The incidences of digoxin toxicity can be reduced by patient education and appropriate counselling from your health care professional:

• Ensure that the correct dose and regimen are taken - missed doses should be avoided but should be taken as soon as remembered unless it is close to the next dose. In this case, it should be skipped, and the regular dosing schedule should be resumed. 
• Emphasise the importance of regular checkups with your healthcare professional and blood tests to monitor the effectiveness of the medication and to check for signs of toxicity.
• Recognise potential signs of toxicity by staying informed about the symptoms of digoxin toxicity. 
• Maintaining a consistent diet with regards to potassium-rich foods such as bananas, avocados, sweet potatoes and spinach, as fluctuations in potassium levels can affect digoxin levels. Excessive consumption of high-fibre food can interfere with the absorption of digoxin.
• Check with healthcare professionals for potential interactions with medications, especially new medications.

Summary

Digoxin, a cardiac glycoside extracted from Digitalis purpurea, is primarily used for the treatment of chronic heart conditions and irregular heartbeats. Digoxin helps regulate potassium and calcium to improve heart muscle contraction and enhance blood circulation. 

Despite its benefits, digoxin toxicity poses a significant risk. The triggers of digoxin toxicity include reduced kidney function, low potassium levels, and interactions with certain medications. Symptoms such as visual disturbances, gastrointestinal issues, and cardiac irregularities can indicate digoxin toxicity. Severe cases necessitate hospitalisation, with treatments involving digoxin-specific antibody fragments and the close monitoring of potassium levels. Prevention strategies include maintaining therapeutic levels of digoxin, monitoring kidney function, and staying educated about potential drug interactions. 

By understanding digoxin's effects and toxicity factors, patients and healthcare providers can collaboratively ensure its safe usage.