Digitalis

Digitalis

How digitalis is used

Risks and side effects

Resources

Digitalis is a drug that has been used for centuries to treat heart disease. The active ingredient in the drug is glycoside, a chemical compound that contains a sugar molecule linked to another molecule. The glycoside compound can be broken down into a sugar and nonsugar compound. Though current digitalis drugs are synthetic, that is, artificially made, early forms of the drug were derived from a plant.

Digitalis is a derivative of the plant Digitalis purpurea, or purple foxglove. The plant’s name, Digitalis (from the Latin digit, finger) describes the finger-shaped purple flowers it bears. English physician William Withering (1741–1799), who experimented with the extract in fowls and humans, first observed the effects of the plant extract on the heart in the late eighteenth century.

Withering’s keen interest in botany led him to collect plant specimens, as did his love for one of his patients (whom he married), a flower painter. Withering noted that old country women used foxglove to treat dropsy (edema), an accumulation of fluids caused by a failing heart. Willing to consider these old wives’tales, Withering embarked on a detailed study of digitalis. He determined the most effective treatment form—a powder made from dried leaves picked just before the plant blossomed—and, of critical importance, the correct dosage for different cardiac conditions. Equally important, Withering established clear standards for when to discontinue administration of the drug, which can be toxic when used in excessive amounts.

Withering reported his results in a treatise entitled, “The Foxglove and an Account of its Medical Properties, with Practical Remarks on Dropsy.” His explanations of the effects of foxglove on the heart have not stood up to the test of time, but his prediction that it could be “converted to salutary ends” certainly has. Indeed, digitalis remains the oldest drug in use for the treatment of heart disease, as well as the most widespread, in use today.

The active principles of digitalis eluded researchers until the mid-1800s. French scientists Augustin Homolle and Theódore Ouevenne won a cash prize in 1844 from the Societe de Pharmacie in Paris (France) when they isolated digitalin. Oscar Schmiedeberg (1838–1921) isolated the highly potent digitoxin in 1875. English chemist Sydney Smith obtained digoxin from woolly foxglove (Digitalis lanata ) in 1930.

The digitalis drugs come in many forms, differing in their chemical structure. As a group, they are classified as cardiac inotropes. Cardiac, of course, refers to the heart. An inotrope is a substance that has a direct effect on muscle contraction. Positive inotropism is an increase in the speed and strength of muscle contraction, while negative inotropism is the opposite. Digitalis has a positive inotropic effect on the heart muscle.

How digitalis is used

Digitalis is used to bolster the ailing heart in congestive heart failure. In this condition, the heart muscle has stretched while straining to pump blood against a back pressure. The back pressure may be caused by high blood pressure, or it may be the result of a leak caused by a faulty aortic valve or a hole in the wall (septum) dividing the right and left halves of the heart. When these conditions occur, the heart muscle, or myocardium, must exert greater and greater pressure to force blood through the body against the resistant force. Over time, the strain will stretch the heart muscle, and the size of the heart increases. As the heart muscle changes in these ways, its pumping action becomes less and less effective. Congestive heart failure occurs when the myocardium has been stretched too far. At this juncture the patient must have a heart transplant or he/she will die.

The administration of digitalis, however, can forestall the critical stage of the disease. Digitalis has a direct and immediate effect on the myocardium. By a mechanism not well understood, digitalis increases the levels of intracellular calcium, which plays an important role in the contraction of the muscles. Almost as soon as the drug has been administered, the heart muscle begins to contract faster and with greater force. As a result, its pumping efficiency increases and the supply of blood to the body is enhanced. Digitalis also tends to bring about a decrease in the size of the ventricles of the failing heart as well as a reduction in wall tension.

In addition to its immediate effect on the heart muscle, the drug affects the autonomic nervous system, slowing the electrical signal that drives the heartbeat. As heart contractions become more efficient, the heart rate slows. For this reason, the drug is said to have a negative chronotropic effect (the prefix chrono refers to time).

As digitalis stabilizes the myocardium, appropriate steps can also be taken to correct the original cause of the disease, if possible. The patient’s blood pressure can be lowered with medications, or heart surgery can be performed to replace a faulty valve or patch a hole in the septum. When it is not possible to improve cardiac function by other means, the patient can be maintained on digitalis for many years.

Risks and side effects

The effect of digitalis is dose related. The higher the dose, then the more pronounced the cardiac reaction. The immediate and direct effect of the drug dictates that the physician closely monitor the patient and adjust the digitalis dosage as needed to provide the corrective effect. At the same time, the physician should be careful not to institute a toxic reaction. Digitalis is a very potent and active drug and can quickly create an overdose situation if the patient is not closely watched. In the case of an overdose, the patient’s heart will begin to beat out of rhythm (arrhythmia) and very rapidly (tachycardia). In addition, the drug may affect the nervous system and cause headaches, vision problems such as blurring and light sensitivity, and sometimes convulsions.

Withering already recognized the toxicity of digitalis and warned against the careless administration of the drug in too high a dose. Despite Withering’s warnings, physicians in the early nineteenth century often overdosed their patients. Consequently, the drug was

KEY TERMS

Aortic valve— The one-way valve that allows blood to pass from the heart’s main pumping chamber, the left ventricle, into the body’s main artery, the aorta.

Cardiologist— A physician who specializes in the diagnosis and treatment of heart disease.

Myocardium— The heart muscle.

Oxygenation— The process, taking place in the lungs, by which oxygen enters the blood to be transported to body tissues.

Septum— The wall that divides the right side of the heart (which contains used blood that has been returned from the body) from the left side of the heart (which contains newly oxygenated blood to be pumped to the body).

considered too dangerous for the greater part of the nineteenth century and was used little. Later in the same century, however, the beneficial properties of digitalis were reassessed, and the drug became an essential element in the cardiologist’s pharmacopeia.

Other drugs to treat diseases have been developed over time, of course, but none has replaced digitalis as the standard therapy for heart failure. A drug of ancient lineage, digitalis remains one of the most reliable and most used medicines.

Resources

BOOKS

Beers, Mark H., et al., eds. The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2006.

The Complete Drug Reference: Micromedex, Thomson Healthcare and U.S. Pharmacopeia. Yonkers, NY: Consumer Reports Books, 2001.

Larson, Litin, Scott C., ed. Mayo Clinic Family Health Book. New York: HarperResource, 2003.

Larry Blaser