# 1911 Encyclopædia Britannica/Digitalis

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​DIGITALIS. The leaves of the foxglove (q.v.), gathered from wild plants when about two-thirds of their flowers are expanded, deprived usually of the petiole and the thicker part of the midrib, bitter taste; and to preserve their properties they must be kept excluded from light in stoppered bottles. They are occasionally adulterated with the leaves of Inula Conyza, ploughman’s spikenard, which may be distinguished by their greater roughness, their less divided margins, and their odour when rubbed; also with the leaves of Symphytum officinale, comfrey, and of Verbascum Thapsus, great mullein, which unlike those of the foxglove have woolly upper and under surfaces. The earliest known descriptions of the foxglove are those given by Leonhard Fuchs and Tragus about the middle of the 16th century, but its virtues were doubtless known to herbalists at a much remoter period. J. Gerarde, in his Herbal (1597), advocates the use of foxglove for a variety of complaints; and John Parkinson, in the Theatrum Botanicum, or Theater of Plants (1640), and later W. Salmon, in The New London Dispensatory, similarly praised the remedy. Digitalis was first brought prominently under the notice of the medical profession by Dr W. Withering, who, in his Account of the Foxglove (1785), gave details of upwards of 200 cases chiefly dropsical, in which it was used.
Digitalis contains four important glucosides, of which three are cardiac stimulants. The most powerful is digitoxin C$_{34}$H$_{54}$O$_{11}$, an extremely poisonous and cumulative drug, insoluble in water. Digitalin, C$_{35}$H$_{56}$O$_{14}$, is crystalline and is also insoluble in water. Digitalein is amorphous but readily soluble in water. It can therefore be administered subcutaneously, in doses of about one-hundredth of a grain. Digitonin, on the other hand, is a cardiac depressant, and has been found to be identical with saponin, the chief constituent of senega root. There are numerous preparations, patent and pharmacopeial, their composition being extremely varied, so that, unless one has reason to be certain of any particular preparation, it is almost better to use only the dried leaves themselves in the form of a powder (dose 1/2-2 grains). The pharmacopeial tincture may be given in doses of five to fifteen minims, and the infusion has the unusually small dose of two to four drachms—the dose of other infusions being an ounce or more. The tincture contains a fair proportion of both digitalin and digitoxin.
Digitalis leaves have no definite external action. Taken by the mouth, the drug is apt to cause considerable digestive disturbance, varying in different cases and sometimes so severe as to cause serious difficulty. This action is probably due to the digitonin, which is thus a constituent in every way undesirable. The all-important property of the drug is its action on the circulation. Its first action on any of the body-tissues is upon unstriped muscle, so that the first consequence of its absorption is a contraction of the arteries and arterioles. No other known drug has an equally marked action in contracting the arterioles. As the vaso-motor centre in the medulla oblongata is also stimulated, as well as the contractions of the heart, there is thus trebly caused a very great rise in the blood-pressure.
The clinical influence of digitalis upon the heart is very well defined. After the taking of a moderate dose the pulse is markedly slowed. This is due to a very definite influence upon the different portions of the cardiac cycle. The systole is not altered in length, but the diastole is very much prolonged, and since this is the period not only of cardiac rest but also of cardiac “feeding”—the coronary vessels being compressed and occluded during systole—the result is greatly to benefit the nutrition of the cardiac muscle. So definite is this that, despite a great increase in the force of the contractions and despite experimental proof that the heart does more work in a given time under the influence of digitalis, the organ subsequently displays all the signs of having rested, its improved vigour being really due to its obtaining a larger supply of the nutrient blood. Almost equally striking is the fact that digitalis causes an irregular pulse to become regular. Added to the greater force of cardiac contraction is a permanent tonic contraction of the organ, so that its internal capacity is reduced. The bearing of this fact on cases of cardiac dilatation is evident. In larger doses a remarkable sequel to these actions ​may be observed. The cardiac contractions become irregular, the ventricle assumes curious shapes—“hour-glass,” &c.—becomes very pale and bloodless, and finally the heart stops in a state of spasm, which shortly afterwards becomes rigor-mortis. Before this final change the heart may be started again by the application of a soluble potassium salt, or by raising the fluid pressure within it. Clinically it is to be observed that the drug is cumulative, being very slowly excreted, and that after it has been taken for some time the pulse may become irregular, the blood-pressure low, and the cardiac pulsations rapid and feeble. These symptoms with more or less gastro-intestinal irritation and decrease in the quantity of urine passed indicate digitalis poisoning. The initial action of digitalis is a stimulation of the cardiac terminals of the vagus nerves, so that the heart’s action is slowed. Thereafter follows the most important effect of the drug, which is a direct stimulation of the cardiac muscle. This can be proved to occur in a heart so embryonic that no nerves can be recognized in it, and in portions of cardiac muscle that contain neither nervecells nor nerve-fibres.
The action of this drug on the kidney is of importance only second to its action on the circulation. In small or moderate doses it is a powerful diuretic. Though Heidenhain asserts that rise in the renal blood-pressure has not a diuretic action per se, it seems probable that this influence of the drug is due to a rise in the general blood-pressure associated with a relatively dilated condition of the renal vessels. In large doses, on the other hand, the renal vessels also are constricted and the amount of urine falls. It is probable that digitalis increases the amount of water rather than that of the urinary solids. In large doses the action of digitalis on the circulation causes various cerebral symptoms, such as seeing all objects blue, and various other disturbances of the special senses. There appears also to be a specific action of lowering the reflex excitability of the spinal cord.
Digitalis is used in therapeutics exclusively for its action on the circulation. In prescribing this drug it must be remembered that fully three days elapse before it gets into the system, and thus it must always be combined with other remedies to tide the patient over this period. It must never be prescribed in large doses to begin with, as some patients are quite unable to take it, intractable vomiting being caused. The three days that must pass before any clinical effect is obtained renders it useless in an emergency. A certain consequence of its use is to cause or increase cardiac hypertrophy—a condition which has its own dangers and ultimately disastrous consequences, and must never be provoked beyond the positive needs of the case. But digitalis is indicated whenever the heart shows itself unequal to the work it has to perform. This formula includes the vast majority of cardiac cases. The drug is contra-indicated in all cases where the heart is already beating too slowly; in aortic incompetence—where the prolongation of diastole increases the amount of the blood that regurgitates through the incompetent valve; in chronic Bright’s disease and in fatty degeneration of the heart—since nothing can cause fat to become contractile.