In tabes dorsalis, intra-spinal, and in paresis, intra-ventricular injections, both being local applications, are yielding better results than have been obtained by any previous method of treatment. In all patients, however, the real results of treatment must be established by means of the Wassermann test. The organic preparations of arsenic have been employed also in the treatment of trypanosomiasis, relapsing fever, Vincent's angina, pellagra, splenic anæmia and leukæmia with results concerning which a definite opinion cannot be expressed at this time.

Furunculosis may be successfully treated by the persistent use of arsenic, and small doses of it are said to have a curative effect upon warts. Given in association with the bromides, it is useful in lessening or preventing the disfiguring acne which so frequently results from the continued administration of these drugs.

The springs of Levico and La Bourboule contain arsenic trioxide. Strong Levico contains 0.005 gm. (112 gr.) of arsenic trioxide and 2 gm. (30 gr.) of iron to 500 mils (1 pt.); weak Levico, 0.0005 gm. (120 gr.) and 0.50 gm. (8 gr.) respectively. La Bourboule contains 0.005 gm. (12 gr.) of arsenous acid and a trace of iron to 500 mils (1 pt.). These waters should always be taken with the meals.

TOXICOLOGY

Acute Poisoning.-Arsenic is used to a very considerable extent for poisonous purposes. The forms most employed are Scheele's and Paris Green (cupric arsenite), and Schweinfurth's Green (a compound of cupric arsenite and arsenate). Symptoms. As the pathology of the effects of arsenical salts in the alimentary canal is practically the same as that of Asiatic cholera, so the symptoms of poisoning by them generally resemble very closely those met with in that disease. Large doses frequently produce no distress for a considerable time, but in the course of half an hour, or perhaps longer, the patient experiences a sense of constriction in the fauces, with dysphagia. About the same time he begins to suffer from slight epigastric pain, which soon becomes extreme, and spreads over the abdomen. It is accompanied with faintness, nausea and excessive vomiting, and later by profuse watery diarrhoea, with tenesmus and intense thirst. The matter vomited and the stools may contain blood, but this is not infrequently absent. The patient also suffers from muscular cramps, headache and dizziness, and gradually sinks into collapse, with coldness of the extremities, pallor, small and feeble pulse, and sighing respiration. This condition passes into one of coma, followed by death, which may or may not be preceded by convulsions. Exceptionally the only symptoms were those of collapse and coma. Death may perhaps occur within twenty-four hours, but more commonly the vital powers are not exhausted

for considerably longer than this, and the patient may linger for several days. Not infrequently it is found that he may recover from the acute symptoms only to develop those of chronic arsenical poisoning.

Post-mortem.-The mucous membrane of the gastro-intestinal tract is generally red and swollen, while its epithelial coat in many places can be readily detached and is found to be in a state of fatty degeneration. As a rule, no erosion is observed unless the arsenic has been swallowed in powder-form when, if the latter has remained for some time in contact with the wall of the stomach, there may perhaps be some erosion, as well as more marked congestion, as the result of its local action. In the intestine the swelling and congestion of the mucous membrane is most pronounced around Peyer's patches, and the bowel generally contains a considerable quantity of thin fluid with flakes of membrane, like the rice-water discharges of cholera. Hæmorrhage is only occasionally met with, but in both the stomach and intestine small particles of arsenic are not infrequently observed. Treatment. It is important that the stomach should be completely emptied as soon as possible, either by washing it out or the use of emetics (see p. 380), choice being made of those least depressing and least irritating. On account of the insolubility of arsenic it is advisable that the stomach washing should be continued for some time. At the same time large quantities of freshly prepared ferric hydroxide with magnesium oxide (see p. 93) or ferric hydroxide (not official) should be given at once; if these cannot be obtained, magnesia, preferably light magnesia, shaken up with water. The antidote must be repeated at intervals so long as the acute symptoms continue. If neither magnesia nor the iron preparations are procurable, dependence must be placed on large doses of castor oil, and water. For the collapse, subcutaneous injections of brandy or ether may be given, and warm applications made to the abdomen and extremities.

Chronic Poisoning.—When arsenic is given medicinally, too large doses may induce slight symptoms of poisoning, such as abdominal pain, loss of appetite, nausea, indigestion, mild diarrhoea, puffiness of the eye-lids, injection of the conjunctiva, and watering of the eyes and nose.

Cutaneous eruptions are also sometimes caused, and while these may be due in part to circulatory derangements, they are believed to result chiefly from a direct action of the drug on the skin. They may be erythematous, papular, vesicular or pustular in character, and may be attended with erysipelatous swelling. Herpes zoster, it is said, has been caused by its prolonged administration. As arsenic is very extensively used in the arts, particularly in the manufacture of wall papers and fabrics, accidental poisoning is not infrequent among workers in arsenic and may occur in persons using articles which contain it. The evidence in regard to chronic poisoning from occupancy of rooms decorated with arsenical wall paper is contradictory, but its possibility cannot be denied. Quite as often the poisoning is due to the arsenic which is a contamination of aniline dyes as it is to the arsenical pigments, so that the color should not be depended upon for an opinion, but rather a chemical examination made.

As the arsenical poisoning goes on, a catarrhal condition of the mucous membrane of the nose and throat is developed, with much sneezing and coughing, cutaneous eruptions of various kinds appear, and, in some instances, a curious pigmentation of the skin occurs (arsenic melanosis); while eventually the hair and

nails fall out. Swelling of the liver, with jaundice, is sometimes met with, and the later phases of the disorder are characterized by sensory and motor disturbances in localized areas, generally in the hands and feet, the result of a polyneuritis. There are acute pains and formication in the extremities, followed by sensory paralysis, with symptoms resembling those of locomotor ataxia. This again is succeeded by motor paralysis, which as a rule is confined to the extremities, but may possibly invade the trunk. It is generally symmetrical and the affected muscles, more commonly the extensors than the flexors, atrophy quite rapidly. Herpes of the face or trunk, of nervous origin, is a common symptom. In very prolonged instances the patient may sink into an apathetic, semi-idiotic condition, or may become epileptic. After death from chronic poisoning, in addition to the gastro-intestinal and nervous lesions, there is found fatty degeneration of most of the organs of the body, and particularly of the liver, kidneys, stomach and muscles, including those of the heart.

DIVISION III.-DRUGS ACTING ON THE CARDIAC MECHANISM

While it was formerly supposed that the spontaneous impulses originating in the heart, which normally commence in the sinus. venosus and extend downward over the auricle and ventricle to the apex, had their origin in the cardiac ganglia, the real function of these ganglia, which may possibly be a nutritive one, is still practically unknown, and there is now at command considerable evidence to the effect that it is in consequence of impulses originating in themselves that the muscular fibres contract. The contractile function of the muscular fibres is, however, subject to two opposing influences, one that of the accelerator nerve-fibres connected with the sympathetic, which tends to augment it, and the other that of the pneumogastric, or vagus, which tends to inhibit it. In studying the effects of drugs on the heart, therefore, all that we are called upon to consider is their action on the muscular structure of the heart, on the nerve-fibres distributed to it from the vagus and the sympathetic, and on the vagus and accelerator centers in the medulla which are extremely sensitive to afferent impulses conveyed from various parts of the body, as well as from the heart itself. Our knowledge of the action of drugs upon the human heart is necessarily somewhat imperfect, since it is principally derived from laboratory experimentation, in connection with which there are many difficulties and sources of error. Thus, many experiments cannot be satis

factorily made upon the mammalian heart, and hence the coldblooded animals have been made use of to a large extent, it is a question how far deductions from these experiments are applicable to the human heart. A uniformity of effect will naturally go far to establish the character of any given action as regards man, but in general we have to depend largely on probabilities in this matter. Attention may here be directed to one point of interest; the action of a large dose of a drug is, as a rule, the opposite of that of a moderate dose.

A. Drugs Acting Upon the Heart Directly. Our knowledge of these has been derived from the application to the heart of a solution of the drug externally, or by means of a transfusion canula, and by the action of the drug upon the excised heart or section of a heart. Since the apex probably contains no nerves, it is customary to conclude that if a drug has an action on the isolated apex it acts exclusively upon the muscle; but as it is always a difficult matter to decide whether a drug acts upon the muscle fibre itself or upon the fine nerves between the fibres, it will be found advisable to make no attempt to distinguish between these actions. In studying the nervous influences affecting the heart's action much more attention has been paid to the inhibitory or vagus than to the accelerating mechanism. The effect of stimulating the muscle is the same as that of stimulating the accelerator fibres, and consists in an augmentation of either the rate or the force of the beat, or both. On the other hand, stimulation of the vagus fibres or its cardiac terminations may cause a diminution in either the rate or the force of the beat, or both; while the paralyzing of either the accelerator or vagus terminations naturally produces an effect just the opposite to that of their stimulation. As it is very difficult to decide whether drugs act upon the muscle or on the nerve-endings, it will be most convenient to classify those which act locally on the heart, by the effect they produce, without reference to this point.

Drugs increasing the force of the contraction:

(1) Digitalis.

(2) Strophanthus.

(3) Squill.

(5) Suprarenal gland.

(4) Caffeine.

(6) Sparteine.

(7) Oxygen.

(8) Camphor.

In frogs these drugs, in large doses, always stop the heart systole; in mammals this may be in diastole with some, e.g., digitalis. They all slow the pulse.

Camphor, musk and physostigmine have the same action without the final arrest in systole. The rate of the pulse is not so markedly altered. Pilocarpine slows the pulse rate but does not increase its force.

Drugs the chief action of which is to decrease the force of the contraction, usually with stoppage in diastole:

(1) Diluted acids.

(2) Strong solutions of salts of the

alkaline metals.

(3) Strong solutions of copper double salts.

(4) Strong solutions of zinc double salts.

(5) Strong solutions of hydrated chloral.

(6) Pilocarpine.

(7) Apomorphine.
(8) Emetine.

(9) Salicylic acid (large doses).

Drugs an important action of which is to increase the rate of the cardiac beat:

Drugs which increase both the force and the number of beats:

Drugs which decrease both the force and the number of the beats:

(1) Aconite.

(4) Antimony salts.

(2) Hydrocyanic acid.

(3) Veratrum Viride.

(5) Hydrated Chloral.

Other drugs possess a similar action but are not ordinarily employed for this purpose as Ipecac, acetanilid, acetphenetidin, antipyrine, lobelia, and ergot.

B. Drugs Acting on the Vagus Center. It may be concluded that a drug acts on the vagus center when it is found that while it has the effect of altering the beat of the heart, such alteration may be counteracted either by section of the vagi or by stimulation of the peripheral end of the nerve, if only one of the vagi be cut.

Drugs which stimulate the vagus center: that is slow the pulse, but this disappears on section of the vagi:

(1) Chloroform.

(2) Hydrated Chloral.

(3) Aconite.

(4) Veratrum Viride.

(5) Digitalis.

(6) Sparteine.

(7) Strophanthus.

(8) Oxygen.

(9) Squill

(10) Staphisagria.

(11) Hydrocyanic acid.

(12) Atropine.

(only very early

(13) Hyoscyamine in their action).