Digitalis

Generic name: Digitalis Lanata Ehrh, Digitalis Purpurea L.
Brand names: Dead Man's Bells, Digitalis, Fairy Cap, Fairy Finger, Foxglove, Lady's Thimble, Lion's Mouth, Purple Foxglove, Scotch Mercury, Throatwort, Witch's Bells, Woolly Foxglove

Usage of Digitalis

Cardiovascular effects

Cardiac glycosides possess positive inotropic effects due to inhibition of sodium-potassium adenosine triphosphatase, which allows calcium to accumulate in myocytes leading to enhanced cardiac contractility. These drugs also possess some antiarrhythmic activity, but will induce arrhythmias at higher dose levels.(Hauptman 1999, Keenan 2005, Kuate 2008)

Animal data

Studies in animals center largely on evaluations of individual chemical compounds on isolated cardiac and other tissues.(Hauptman 1999, Keenan 2005, Navarro 2000)

Clinical data

Digitalis glycosides have been used clinically for the treatment of heart failure for more than 200 years and remain the source of commercial digoxin preparations; however, a defined place in therapy remains under debate. Reviews of the large, multicenter Digitalis Investigation Group trial and other clinical trials have found no clear effect of digitalis on mortality in heart failure. Some effect has been demonstrated for secondary outcomes of decreased hospitalizations and clinical (symptomatic) deterioration.(Feussner 2010, Hood 2004) For further information, consult standard pharmacology references.

Other effects

In vitro experiments and screening studies have shown cytotoxic properties of glycosides and flavonoids from D. purpurea and D. lantana. Activity against human cancer cell lines, including solid tumor lines, has been demonstrated. Mechanisms include direct cytotoxicity resulting in apoptosis, inhibition of aflatoxin-induced cytotoxicity, inhibition of induction of nitric oxide synthase, and increases in glutathione S-tranferase.(Choi 2005, Johansson 2001, Lee 2006, Lindholm 2002, López-Lázaro 2003)

A study in hyperglycemic and dyslipidemic rats demonstrated enhanced glucose tolerance 2 hours after the rats were given a single dose of the saponin digitonin. Positive effects on the lipid profile were also observed.(Ebaid 2006)

Antileishmanial activity has been demonstrated in mice with the administration of beta-acetyl-digitoxin extracted from D. lanata leaves. Anti-Leishmania IgG2a antibody was significantly higher in mice treated with the extract and with the polymeric micelle-extract formulation with the highest IgG2a antibodies induced with the latter.(Freitas 2021)

Digitalis side effects

Adverse reactions are generally related to toxicity.

Before taking Digitalis

Documented adverse cardiac reactions. Avoid use.(McGuffin 2997)

How to use Digitalis

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.Ebaid 2006, Hood 2004

Warnings

All parts of the plant are toxic. Animal toxicity occurs during grazing. Children have become ill by sucking the flowers or ingesting seeds or parts of the leaves. Deaths have been reported among people who drank tea made from digitalis mistakenly identified as comfrey, although the bitter taste often deters ingestion, and its emetic properties can induce vomiting, thereby limiting systemic absorption. Digitalis poisoning is also associated with intentional ingestion with suicidal intent.Jowett 2002, Lacassie 2000, Lin 2010

Digitalis glycosides accumulate and are excreted slowly; therefore, intoxications during therapy are common. The incidence of digitalis toxicity has been estimated to range from 5% to 23%. More stringent dosing guidelines and monitoring techniques have dramatically reduced the incidence of therapeutic overdose.

Signs of plant or purified drug poisoning include blurred vision, contracted pupils, dizziness, excessive urination, fatigue, muscle weakness, nausea, strong but slowed pulse, tremors, and vomiting; in severe cases, stupor, confusion, convulsions, and death can occur. Cardiac signs include atrial arrhythmias and atrioventricular block. Chronic digitalis intoxication is characterized by visual halos, yellow-green vision, and GI upset.Dick 1991, Hauptman 1999, Jowett 2002, Morton 1977

In mild cases of toxicity (atrial fibrillation with a slow ventricular response or occasional ectopic beats), temporary withdrawal of the drug and electrocardiogram monitoring is sufficient.Trease 1989 Gastric lavage or emesis together with supportive measures, such as electrolyte replacements, antiarrhythmics (eg, lidocaine, phenytoin), and atropine, have been used to manage acute poisonings. Digoxin-specific Fab antibody fragments may be used in managing acute intoxications caused by digitalis and related cardioactive glycosides; however, their efficacy remains unproven by controlled clinical trials.Hauptman 1999, Lacassie 2000, Roberts 2006, Wickersham 2004

In an analysis of the Nurses’ Health Study, long-term use (more than 4 years) of digitalis (as digoxin) has been linked to an increased risk of invasive breast cancer, although conclusive evidence of causality is lacking.Ahern 2017, Xu 2013

What other drugs will affect Digitalis

There are numerous interactions with digoxin and digitalis glycosides, ranging from relatively minor (eg, cimetidine, triamterene) to life threatening. Many of the life threatening interactions occur as a result of elevated digoxin serum levels (eg, amiodarone, cyclosporine, macrolide and tetracycline antibiotics, propafenone, quinidine, verapamil) or electrolyte disturbances (eg, diuretics).Tatro 2004 For more comprehensive information on digitalis drug interactions, refer to standard drug interaction texts.

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