Foxglove, Digitalis purpurea. Universally official.

Pharmacology

What is here given is applicable to the digitalis series, not merely to digitalis. These have a common action on the heart, with variations in other directions. Their cardiac effects are due to glucosides having a common action; and squill, which is also emetic, is the member of the series having the most definite side-action.

Digitalis, chemically considered, is a wonderful plant, literally dozens of proximates and alleged proximates having been broken out of it. Only the more definite ones will be considered - at the close of this article - the tendency being to return to the preparations of the whole drug.

Very unfortunately, the galenical preparations vary immensely in activity and it is quite essential that liquid preparations be assayed and physiologically standardized. Most good pharmaceutical manufacturers are doing this.

The members of the group are: Digitalis, stro-phanthus, squill, helleborus niger, convallaria, adonis, nerium, euonymus, antiaris, thevetia, cheiranthus, coronilla, tanghinia, apocynum, and erythrophloeum. Some of these are quite unsuited for use as drugs.

The whole group possess locally irritant properties to a greater or less degree, are partly broken down in the alimentary canal, are absorbed rather slowly, and are cumulative.

The heart action is a slowing of the rhythm, the systole soon becoming more complete and the diastole oppositely affected; then heart-block appears, the ventricle contracting after every alternate auricular contraction. Ultimately, the ventricle is arrested in systole, while the auricles continue to beat for some time. This order of phenomena may vary somewhat under different dosage.

The first or therapeutic stage of digitalis action requires some further comment. There is an increase in amplitude of the beat and volume output, especially in the exhausted heart. The auricular contraction is strengthened, with a slight decrease in diastolic relaxation (Straub). There are other minor influences; but the output per beat and per minute is increased; and, more particularly in the mammalian heart, the heart is slowed, owing to a central stimulation of the vagus, the ventricles empty themselves more completely than formerly, and diastole may be either diminished or increased; the beat becomes more regular (Clark).

The digitalis group of drugs, in sufficient dosage, produce vaso-constriction (more with digitoxin than with strophanthin) and raise blood-pressure. It is to be remarked here that in man the ordinary therapeutic doses do not raise blood-pressure. This is well proven by several recent investigators.

There is little action on renal secretion in the normal animal; but the increase in the cardiac output induces marked diuresis in certain diseases.

All of the digitalis group of drugs are more or less of gastro-intestinal irritants, squill being an emetic, and euonymus a purgative.

The action on the heart muscle is purely selective, other muscular tissue not being influenced.

No active preparation of digitalis is yet known which can be injected under the skin without causing more or less pain and inflammation (Dixon).

In large doses the lower centers of the brain and the vagus are stimulated; and vomiting may be induced.

Hatcher and others have shown that, even with standardized products, the absorption is irregular, varying immensely in different individuals and with various members of the digitalis group. For instance: Tincture of strophanthus, when injected or tested upon an isolated heart, is found to be forty times as strong as is tincture of digitalis; but, when administered by mouth, digitalis is more efficient than strophanthus. This is wholly due to the fact that the digitalis glucosides are the more readily absorbed. A good method to induce relatively prompt absorption from the stomach is to administer a strongly alcoholic preparation upon a small piece of bread.

Hatcher, Fraenkel, and others have investigated the cumulative action and have reached no definite conclusion as to its cause.

Therapeutics Of Digitalis

As Mackenzie has shown, the most valuable results are obtained in cases of auricular fibrillation, digitalis inducing efficient ventricular action.

A heart stimulant is demanded when undue relaxation occurs, as when valvular insufficiency or stenosis permits venous accumulation of blood. An increase in the work of the heart relieves these conditions, and digitalis induces this increased work. The first vessels to be influenced are those of the heart itself, thus improving its nutrition; so the beneficial effect is vital as well as mechanical.

In cardiac ascites digitalis leaves, 1 grain; squills, 1 grain; blue mass, 2 grains is the old and effective.

Matthew Baillie combination never improved upon. The same can be used in ordinary cardiac edema, or caffeine may be given with the digitalis. In cardiac weakness in febrile diseases, digitalis rarely is of value, and may do harm; but a possible exception is in the later stages of lobar pneumonia. In complete heart block digitalis is nearly always indicated.

Dyspnea of cardiac origin is successfully met with digitalis, as may also be met dyspnea horn, fibrosis of the lung, of course with other appropriate medication.

In valvular disease, especially with the pulse over 80 per minute, with weak contraction, dilatation and anasarca, digitalis is exceedingly useful, more especially in mitral disease. Digitalis is especially indicated in auricular fibrillation, which is very common in mitral cases.

In chronic myocarditis and fibroid degenerations the drug should be given with care. Aortic insufficiency is another disease in which it is useful only if carefully watched. Keep these patients in bed while giving full digitalis dosage. The presence or absence of auricular fibrillation is a good guide.

Paroxysmal tachycardia is not a disease responding well to treatment. Usually the intravenous administration of strophanthin gives better results than does digitalis, but some cases respond fairly well to digitalis. Bradycardia is so often due to underlying causes requiring mercury or the salicylates that the use of digitalis is of secondary interest, though it may be demanded.

Digitalis is useless in cases of recent inflammation of the heart, as from acute rheumatic fever, and may be harmful. But in the treatment of septicemia digitalis is a valuable symptomatic remedy.

Undue slowness of the pulse contraindicates digitalis. Forcible apex-beat and throbbing arteries also contraindicate heart stimulants.

Degenerated arterial coats do not contraindicate the use of digitalis, as was formerly taught, for therapeutic doses of digitalis rarely raise blood-pressure. There is no occasion to combine nitrites with digitalis in these cases.

Auricular fibrillation being the indication for digitalis, it is necessary that physicians recognize its presence. It requires the study of a recent textbook fully to understand the condition, but, briefly, an irregularly irregular pulse is a leading symptom of auricular fibrillation. It is more pronounced when the pulse is fast. In mitral stenosis a presystolic bruit disappearing indicates the onset of auricular fibrillation; a diastolic bruit persists. There is the ventricular form of venous pulse, best shown with the polygraph. Clinically, when auricular fibrillation exists, digitalis rapidly reduces the pulse rate except in cardiosclerosis and pyrexia.

Administration

In general, large doses produce prompt results - with certain disadvantages. So soon as these disadvantages - nausea, vomiting, headache, diarrhea, etc. - appear, cut down the dose. But, if a patient really needs digitalis, get him under its influence, and then maintain with moderate dosage. Or drop out the drug for a few days and then resume. As much as 2 fluidrachms of digitalis tincture has been given in one day to impress initially a serious case, but this is to be regarded as a maximum. Keep the patient in bed while giving large doses. Look out for "coupling of the beats" and a pulse below seventy.

Digitalis leaves, average dose, 1 grain; extract, 1-5 grain; fl., 1 minim; tincture, 15 minims (rather high); infusion, 1 fluidrachm.

Digitalis Principles And Newer Products

These are honest and scientific products; but it is very questionable if these proprietary preparations possess any advantages over assayed and standardized official preparations.

Digitalein, Crude

A mixture of glucosides. Dose: 1-60 to 1-30 grain 2 or 3 times a day. Digi-talin, True - an active drug given in dosage a little greater than digitoxin. The French Digitalin has an action like digitoxin. Dose: 1-250 to 1-35 grain. Digitalin, "German" - is a mixture of glucosides and may be given in twice the dose of the French. Digitoxin - a very active product. Dose: 1-130 grain. Digipoten - a mixture of digitalis glucosides. Dosage the same as digitalis, each tablet containing 1/2 grain. Digipuratum - free from digitonin. Put up in ampules containing 1 1/2 grains of the drug, and in tablets of same dosage. Digitol - a standardized fat-free tincture. Dose: 5 to 15 minims. Digitone is a similar product, but sealed in glass containers from which the air is exhausted. Digalen is low in alcohol and may be used intravenously in doses not to exceed 15 minims; per os, 8 to 15 minims. Normal Digitalis, fat free.