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Medicinal use and mechanism of action

A group of medicines extracted from foxglove plants are called Digitalin. The use of Digitalis 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,[10] which is considered the beginning of modern therapeutics.[11][12] It 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. Digitalis is hence often prescribed for patients in atrial fibrillation, especially if they have been diagnosed with congestive heart failure. Digoxin was approved for heart failure in 1998 under current regulations by the Food and Drug Administration on the basis of prospective randomized study and clinical trials. It was also approved for the control of ventricular response rate for patients with atrial fibrillation. Recent American College of Cardiology/American Heart Association guidelines recommend digoxin for symptomatic chronic heart failure for patients with reduced systolic function, preservation of systolic function, and/or rate control for atrial fibrillation with a rapid ventricular response. Recent Heart Failure Society of America guidelines for heart failure provide similar recommendations. Despite its relatively recent approval by the Food and Drug Administration and the guideline recommendations, digoxin use is decreasing in patients with heart failure. This is likely the result of several factors. Digoxin has not been promoted by the pharmaceutical industry and has received little attention at national and international meetings, possibly the result of the development and promotion of other, newly patented therapies for heart failure. Also, safety concerns about digoxin therapy–increased mortality in women also may have contributed to this decrease in its use.

A group of pharmacologically active compounds are extracted mostly from the leaves of the second year's growth, and in pure form are referred to by common chemical names such as digitoxin or digoxin, or by brand names such as Crystodigin and Lanoxin, respectively. The two drugs differ in that Digoxin has an additional hydroxyl group at the C-3 position on the B-ring (adjacent to the pentane). Both molecules include a lactone and a triple-repeating sugar called a glycoside.

Digitalis works by inhibiting sodium-potassium ATPase. This results in an increased intracellular concentration of sodium ion and thus a decreased concentration gradient across the cell membrane. This increase in intracellular sodium is then used as a driving force for the Sodium-Calcium pump to bring calcium ions into the cell. This increased cytosolic calcium ion concentration results in increased calcium ion storage in the sarcoplasmic reticulum. Upon action potential (cardiac contraction) more calcium is released from the sarcoplasmic reticulum and this gives a positive inotropic effect (higher contractility). Digitalis also has a vagal effect on the parasympathetic nervous system, and as such is used in reentrant cardiac arrhythmias and to slow the ventricular rate during atrial fibrillation. The dependence on the vagal effect means that digitalis is not effective when a patient has a high sympathetic nervous system drive, which is the case with acutely ill persons, and also during exercise.

Digitalis toxicity (Digitalis intoxication) results from an overdose of digitalis and causes anorexia, nausea, vomiting and diarrhoea, as well as sometimes resulting in xanthopsia (jaundiced or yellow vision) and the appearance of blurred outlines (halos). Bradycardia also occurs. Because a frequent side effect of digitalis is reduction of appetite, some individuals have used the drug as a weight loss aid.

Digitalis is an example of a drug that is derived from a plant that was formerly used by folklorists and herbalists: herbalists have largely abandoned its use because of its narrow therapeutic index and the difficulty of determining the amount of active drug in herbal preparations. 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.

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