of pain. When locally applied, it is a local anesthetic, in 25 per cent. solution, but irritation has followed its hypodermatic use. produce an erythematous or other rash. It may moderately increase arterial pressure, in small doses, by direct stimulation of the heart; in large doses it is a cardiac depressant, the final fall of blood-pressure being certainly due, at least in part, to a direct action upon the heart. Like acetanilid, it is somewhat diuretic, and it is excreted in great part unchanged in combination with sulphuric acid and perhaps with glycuronic acid. It does not cause either a destruction of red cells nor a formation of methæmoglobin in the blood. It rapidly reduces an elevated temperature in the same way as does acetanilid. In large doses it is said to produce convulsions; later, coma and paralysis of motor nerves and muscles.

THERAPEUTICS OF ANTIPYRINE

Antipyrine is given internally as a powerful antipyretic, in fevers of various kinds. It is also used as a hæmostatic in hæmorrhoids and epistaxis, and as an analgesic, when applied locally, in tuberculous laryngitis. It has been given with some success in diabetes mellitus and insipidus. It is largely employed as an anti-neuralgic, relieving the pains of locomotor ataxia and other nervous affections, and it has been highly recommended as a sedative in chorea, whooping cough and epilepsy. As an anti-rheumatic it is not alone effective, but administered contemporaneously with the salicylates is more satisfactory than either when given singly.

TOXICOLOGY

Antipyrine has been credited with a considerable number of deaths, but it is quite likely that most of them have been due to improper dosage. While antipyrine is somewhat less liable to toxic action, it occasionally produces collapse in the same way as does acetanilid. The treatment of the depression caused by it is the same as when produced by the latter.

ACETPHENETIDIN

For the Preparation of Acetphenetidin see p. 110.

ACTION OF ACETPHENETIDIN

Acetphenetidin has no action externally, nor on the gastro-intestinal tract, and with ordinary doses the blood is unaffected. It

slightly depresses the heart, but does not, in ordinary doses, affect the respiration. It is a mild diuretic, and large doses cause the passage of altered blood. It is a powerful antipyretic, by increasing heat dissipation and also diminishing heat production to some extent. It is likewise a powerful analgesic.

THERAPEUTICS OF ACETPHENETIDIN

It is a valuable remedy for reducing fever, and because it depresses the heart but little, it is safer than either antipyrine or acetanilid. It is, however, very insoluble, and slower and less powerful than these remedies, though its effects last longer. Since it possesses a very marked analgesic action, acetphenetidin is to be preferred as a remedy for the relief of pain, as in neuralgia, sciatica, locomotor ataxia, migraine and various headaches. For this purpose, it should be administered every hour for three or four hours; when relief generally results. This drug has been of service in the treatment of epilepsy.

TOXICOLOGY

Acetphenetidin sometimes but very rarely produces severe vomiting, sweating, feeble and rapid pulse, and collapse. Alcoholic stimulation and strychnine hypodermatically are indicated. External warmth is important.

DIVISION VIII.-DRUGS ACTING ON THE RESPIRATION

The influences affecting the respiration are so numerous and varied that it is not always easy to determine the precise mode of action of any drug which produces an impression upon it. Thus, the respiratory center in the medulla, which is subject to direct or reflex influences from almost all the organs of the body, the movements of the respiratory muscles, or the circulatory mechanism influencing the respiration may be acted upon; or, again, alterations produced in the blood or in the air respired may affect the function. In therapeutics, however, the object is generally to remove the cause of or alleviate respiratory difficulty, rather than act upon the respiration itself. Drugs which produce changes in the blood and circulation have already been considered, while for the consideration of such modifica

tions of the temperature, moisture and atmospheric pressure as are of service reference must be made to treatises on general therapeutics. Therefore, the respiratory drugs will now be treated of under the following heads:

A. Drugs altering the Composition of the Air Inhaled.-These are drugs which, when inhaled, have some direct effect on the respiratory mucous membrane, or on the bronchial and pulmonary contents, and may also have remote effects. Certain drugs, although they are not employed for their effects on the respiration, are most conveniently administered by inhalation; e.g., anæsthetics, oxygen and amyl nitrite.

Some drugs when inhaled produce very marked irritation of the bronchial mucous membrane, thus giving rise to vascular dilatation and augmented secretion, and reflexly causing cough from stimulation of the sensory nerves of the part.

Such are iodine, bromine, chlorine, senega, ipecac, nitric acid fumes, and ammonia. These are rarely used therapeutically as inhalations, and their inhalation is to be particularly avoided in irritable conditions of the bronchi.

Some drugs, when inhaled, are soothing, to the bronchial mucous membrane.

Hydrocyanic acid, is such a drug but is rarely employed, if ever, in this way. Inhalations which are used to stimulate the bronchi, that is to say, to increase their vascularity, secretion, and muscular power, are

(1) Phenol.

(2) Oil of cajuput.

(3) Compound tincture of benzoin.

(4) Creosote.

(5) Oil of cubeb.

(6) Spirit of camphor.

Of the first two 1.20 mils (20 m), of the others 15 mils (fl 3 ss) should be added to 500 mils (1 pt.) of water at 60°C. (140°F.).

Inhalations which are used to disinfect foul secretions from the bronchial mucous membrane are those of—

B. Drugs acting on the Respiratory Center.-If, when injected into the carotid artery, a drug produces a very prompt effect on respiration, it is concluded that it acts on the respiratory center. In order to determine whether the drug acts on the center, or on the vagal terminations in the lung, it is customary to divide the vagi and then observe whether it acts in the same way after, as before, the section.

Drugs which directly stimulate the respiratory center are

(1) Ammonia (very powerful).

(2) Strychnine.

(3) Apomorphine.

(4) Belladonna.

(5) Stramonium.

(6) Hyoscyamus.

Drugs which depress the respiratory center are—

(1) Physostigmine (very powerful).

(2) Hydrated chloral.

(3) Chloroform.

(4) Ether.

(5) Alcohol.

(6) Opium.

(7) Hydrocyanic acid.

(8) Codeine.

(9) Aconite.

(10) Veratrine.

(11) Caffeine.

(12) Gelsemium.

(13) Ipecac.

Alcohol, ether, chloroform, caffeine, and quinine slightly excite, before they depress, the respiratory center.

Therapeutics. Drugs exciting the respiratory center may be given, when there is any difficulty in respiration, for the purpose of increasing the force of the respiratory act; at the same time measures should be employed to remove the cause of the difficulty. They are, naturally, most frequently required in respiratory diseases, and especially bronchitis. Ammonia and apomorphine are very frequently prescribed for the reason that they are also powerful expectorants, and belladonna is applicable in instances of excessive bronchial secretion.

Drugs which depress the respiratory center are very seldom required for this action; but the center for the reflex act of coughing is in the immediate vicinity of the respiratory center, and opium, morphine, codeine, hydrocyanic acid, and ipecac are often very valuable in allaying the continual hacking cough frequently accompanying disease of the heart and lungs.

The drugs which relieve cough are very numerous, since this may be reflexly set up by irritation of so many peripheral parts and internal organs, such as the nose, throat, pharynx, ear, teeth, larynx, trachea,

bronchi, lungs, pleura, stomach, and liver; and consequently its successful treatment generally depends upon the removal of local irritation in any of these.

C. Drugs affecting the Bronchial Secretion.

It is probable that volatile oils and substances containing them decrease the amount of bronchial secretion as a later effect.

(b) Those decreasing it:

(1) Acids.

(2) Belladonna.

(3) Stramonium.
(4) Hyoscyamus.

Under some circumstances alkalies may decrease the secretion.

(c) Those disinfecting it: Drugs which, when inhaled, act in this way have already been mentioned. Copaiba, cubeb, eucalyptus, and many volatile oils are excreted partly by the bronchial mucous membrane, and thus will disinfect the secretion in this process.

Therapeutics. In bronchitis, remedies which increase the secretion are used when the latter is so viscid that it adheres to the tubes and cannot be coughed up; and those which decrease it are employed to prevent its formation when it is too abundant to be easily expectorated. The purpose of disinfectants is evident.

D. Drugs relaxing Spasm of the Muscular Coat of the Bronchial Tubes, or Antispasmodics. It is believed that the symptom known as asthma is due to a spasmodic contraction of the bronchial tubes, and as the following relieve this symptom, it is concluded that these drugs relax spasm of the muscular coat of the bronchial tubes.

(1) Stramonium.

(2) Belladonna.

(3) Hyoscyamus.

(4) Grindelia.

(5) Aspidosperma.
(6) Lobelia.
(7) Chloroform.
(8) Ether.

From their analogous action in other parts of the body, it is probable that the following drugs act in the same way: Opium, hydrated chloral, ether, cannabis and amyl nitrite.