This condition of increased tone may be held by judicious use of digitalis for considerable periods of time. Should the limit of safe dosage, however, be overstepped, the poisonous action of digitalis may appear. This poisonous action has been interpreted in a variety of ways, but it would appear that two explanations alone are tenable, perhaps only one. It has been held that one of the first results of poisoning is a partial paralysis of the vagus center, this would let up on the inhibitory rein on the heart and it would commence to beat faster, being still stimulated as to its muscle; further loss of inhibitory control would cause arhythmia, and the end result would be a rapid, irregular heart with loss of tone and final exhaustion.

It has been shown, however, in some instances, and these are yet too few to be positive concerning the matter, that artificial vagus stimulation is effective in slowing the heart even in the last stages of poisoning. Should this be interpreted that the vagus centers are not exhausted by digitalis, in order to explain the symptoms noted, it must be assumed that the muscle stimulation has become so excessive that even the vagus inhibition is ineffectual in controling it, hence the rapid irregular heart-action is a result of intense muscle irritability brought about by the members of this series. According to this view there is, in the final stages of poisoning, a distinct delirium cordis set up which the vagus inhibition is unable to control. This brings about the arhythmia, loss of efficient contractions, and finally exhaustion with marked diastolic relaxation.

The action of digitalis on the blood-vessels is marked. It causes in therapeutic doses a distinct stimulation of the vasoconstrictors with an increase in the arterial tension. An action on the muscles of the arteries themselves augments this central action, probably antedates it. In poisoning the blood-pressure usually falls, but it is apt to be extremely irregular; final toxic stages are invariably accompanied by loss of pressure, both in the interior and in the extremities.

Nervous System. - This is primarily and markedly stimulated In small doses this action is limited to the medulla in the inhibitory cardiac and vasoconstrictor centers; large doses cause a more extended medullary excitation, with nausea and vomiting, convulsions, and increased respirations; toxic doses induce central motor convulsions, which are not due to cerebral anemia, since they may develop while the circulatory blood-supply is ample.

Absorption and Elimination. - Digitalis is more rapidly absorbed than eliminated, the elimination probably taking place by the kidneys. Cumulative action, so called, may take place if the drug is not properly administered.

Kidneys. - Digitalis was introduced into modern practice because of its action as a diuretic.

This diuretic action is due largely to the increase of blood-pressure in the glomeruli of the kidneys, being therefore more pronounced in conditions in which low arterial pressure is maintained at the same time. Very large doses, instead of increasing the amount of urine, may diminish or even wholly suppress it.

Metabolism. - This is increased by reason of the increase in the general circulation. With increased blood-pressure the amount of nitrogen elimination is increased, as is also the quantity of CO2 given off. If the blood-pressure is not raised by the drug, the increase of these is not noted.

Temperature. - Medicinal amounts have no appreciable effect upon the temperature; large doses cause a reduction of bodily heat in febrile conditions, while toxic doses reduce temperature even in health. The action of digitalis upon the circulatory system is retarded by high temperature.

Eye. - Medicinal amounts have no effect. Large or poisonous doses may cause dimness of vision, amblyopia, diplopia, or mydriasis. In a case of poisoning by digitalis recorded by Jeanton there was xanthopsia for two days.

Uterus. - Large doses stimulate contraction in the uterine muscles.

Untoward Action. - Erysipelatous and papular eruptions have been produced by the drug, there having been also observed nausea and a feeling of weakness in the stomach, dimness of vision, headache, heaviness of the head, sleeplessness, and debility.

Poisoning. - Toxic symptoms may occur either from the ingestion of a single poisonous dose or the accumulation of the drug under prolonged administration.

In the more marked cases of poisoning from overdosage there are marked disturbances of the gastro-intestinal tract, abdominal pains, vomiting and purging. The pulse may at first be slowed down to 40, to be followed in the stage of collapse by a rapid, irregular, and compressible pulse - often imperceptible at the wrist - and syncope, more frequently occurring when the patient is raised up.

Other symptoms are - feeble respiration, dilated pupils and occasionally double vision, headache, delirium and stupor, and possibly convulsions just before death, which result from medullary excitation. Digitalis is not a rapid poison, the fatal collapse being usually deferred from ten to forty-eight hours.

The symptoms indicative of the cumulative action of digitalis are usually gastric irritability, headache, and dizziness. These are associated with a feeling of fulness in the vessels, particularly in the temples, by weakness in the pit of the stomach, and by a tendency to syncope. There may also be ringing and buzzing in the ears, and disturbances of sight and hearing.

Poisonous doses are difficult to determine. One teaspoonful of the leaves, as an infusion, and 40 grains of the powder, have caused death, whereas ten times as much in infusion and 80 grains of the powder have not produced fatal results. The extract in 20-grain doses has been lethal, as have also 2 ounces of the tincture. Digi-toxin in 1/30 grain (.002 Gm.) has been deadly, and the commercial digitalins have caused serious results in doses of from 1/2 - 1 grain (.030-.060 Gm.).