Origin. - The monacetyl derivation of aniline.

Description and Properties. - White, shining, micaceous, crystalline laminae, or a crystalline powder, odorless, faintly burning taste, permanent in air, neutral to litmus-paper. It is soluble, at 250 C. (77F.),in 179 parts of water, 2.5 parts of alcohol, 18 parts of boiling water, and in 0.4 part of boiling alcohol; also in 18 parts of ether, and easily soluble in chloroform.

Dose. - 2-10 grains (0.1-0.65 Gin.) [4 grains (0.25 Gm.), U. S. P.], 1 Antifebrin is a copyrighted name for acetanilid or phenylacetamide, as it is sometimes called. Many proprietary remedies sold at comparatively high prices are mixtures of acetanilid and other compounds.

Official Preparation

Pûlvis Acetanildi Compsitus - Plveris Acetanildi Compsiti - Compound Acetanilid Powder (U. S. P.). - A mixture of acetanilid,caffeine, and sodium bicarbonate ; it is a modification of the National Formulary article of the same name and has been known as acetanilid compound (Aulde). The sodium bicarbonate increases the solubility of the acetanilid.

Dose. - Average dose, 7 1/2 grains (0.500 Gm. = 500 milligrammes), U. S. P.

Acetanilid is the cheapest of the common analgesics and it is extensively used in the "headache powders1 "sold under such a variety of names. These powders frequently contain also caffeine and an alkaline salt, usually sodium bicarbonate or ammonium carbonate.

Physiological Action. - Externally and Locally. - Antiseptic, slightly sedative.

Internally. - Digestive System. - Non-irritating, sedative ; medicinal doses sometimes allay nausea.

Circulatory System. - In medicinal doses the arterial tension is slightly raised, while the heart is slowed. Toxic doses directly depress the heart and vasomotor mechanism, causing an immediate fall of arterial pressure and great cardiac depression.

In large doses or when taken for some time in comparatively small doses acetanilid develops the characteristic blood-changes spoken of. Methemoglobin is formed, and in very large doses hemolysis may occur.

Nervous System. - In medicinal doses acetanilid is a sedative to the sensory nerves and spinal cord. Small doses are mildly stimulant to the brain, and under certain conditions the drug is a hypnotic. Toxic doses result in general anesthesia and abolition of reflexes, with paralysis of motor and sensory nerves.

Respiratory System.. - Medicinal doses produce no special effect. When toxic doses are given there is a rapid and labored respiration. Death is produced by respiratory failure, due to direct action of the drug upon the respiratory center, and indirectly by greatly decreasing the oxygen-carrying power of the blood and by paralyzing the peripheral motor nerves.

Absorption and Elimination. - Acetanilid is an active diuretic, increasing the excretion of urea, and to some extent the excretion of uric acid. After toxic doses have been taken the urine becomes dark or brownish in color, from the presence of disorganized corpuscular elements of the blood. Acetanilid is chiefly eliminated by the kidneys as para-amido-phenol combined with acetic, sulphuric, or glycuronic acids.

Temperature. - Acetanilid has little or no effect on the normal body temperature; but if the latter is above normal, the drug has a marked antipyretic action, often reducing the temperature to below normal. This effect of acetanilid, and of the aniline group in general, is due largely to the action of the drug on the heat-governing mechanism. When the body is in a state of hyperpyrexia the heat-governing mechanism is in an irritable condition, owing 1For analysis of a number of these powders, set Jour. Am. Med. Assoc, vol. xliv., p. 1791, I905.

to certain poisons circulating in the blood, and will not respond to the normal limit (98.60 F.) of body temperature. Acetanilid causes this mechanism to respond to a lower temperature, and, through its action on the vasomotor center, stimulates the vasodilators, thereby augmenting the peripheral circulation with consequent increase of heat-dissipation. The exact mechanism is far from being understood.

Eye. - Medicinal doses have no apparent influence on the eye. Toxic doses have produced contracted and motionless pupils.

Untoward Action. - Under prolonged use of acetanilid congestion of the liver, kidneys, and spleen occurs. Paroxysms of sneezing have apparently been induced by a medicinal dose, and, under the same, redness of the skin, chilliness, and cyanosis have sometimes ensued.

Poisoning. - The skin is cyanosed, the face is livid and anxious, and the body is covered with cold sweat. There may be vomiting; the pulse is soft, slow, later rapid, and weak, accompanied by profound prostration. The respirations are first rapid and labored, and later slow and very shallow, death resulting usually from respiratory paralysis. There may be hallucinations, muscle twitch-ings, convulsions from asphyxiation, icterus, and skin eruptions. After death the heart, liver, and kidneys are found in a state of acute fatty degeneration. 7 1/2 grains (0.5 Gm.) given nine times in five days has caused death; 30 grains (2 Gm.) within twenty-four hours has also been fatal, and 1 grain (0.5 Gm.) has caused the death of a one-year-old child.

Treatment of Poisoning. - Diffusible stimulants, like alcohol, in small doses, ammonia, and sulphuric ether. Coffee, atropine, and strychnine hypodermically as circulatory and respiratory stimulants. External heat and, if necessary, oxygen inhalations to overcome cyanosis. Artificial respiration is imperative.

Therapeutics. - Externally and Locally. - Acetanilid has been locally applied for the treatment of chancre and chancroid, but there are other antiseptics which are generally considered to be more satisfactory. It is quite an active hemostatic, and may be used in epistaxis and hemoptysis.

Internally. - The use of acetanilid in fevers has been practically abandoned by the great majority of clinicians. If an antipyretic of this character is indicated at all, it is in sthenic fevers, and then to be used only with great care. Its tendency to cause cardiac depression, profuse sweating, and collapse renders its use harmful, if not unsafe, in low conditions like typhoid fever and advanced phthisis. It may often be administered with good effect in the first stage of pneumonia. The headache, fever, and other unpleasant symptoms in the exanthemata are greatly modified by its use, although when this drug is given to children they must be very carefully watched to avoid untoward effects.

In acute tonsillitis, in influenza, in acute bronchitis, acetanilid is very serviceable.

There is considerable difference of opinion in regard to the utility of acetanilid in rheumatism. Some authorities believe that it exercises a most favorable influence in the acute articular variety, being less apt to disturb the brain than salicylic acid or its salts. The drug certainly mitigates, and often entirely relieves, the pain and swelling, while it reduces the fever. Like salicylic acid, it has no power to prevent heart-complications, but, on the contrary, it should be used with great care, if at all, when such complications exist. It has no tendency to prevent relapses.

The dose of acetanilid in acute rheumatism should not exceed 6 grains (0.5 Gm.) three times a day.

Acetanilid is a very efficient analgesic, and the introduction of this drug, antipyrine, and other remedies of this character has enabled the physician to relieve the pains of certain spinal diseases more efficiently than was possible before.

The crises of locomotor ataxia are often promptly relieved by acetanilid. Neuralgias of every kind indicate its use. The pains of neuritis, lumbago, gastralgia, dysmenorrhea, sciatica, tabes dor-salis, and nearly every kind of headache usually yield to its analgesic influence.

In many cases of chorea and epilepsy (especially the diurnal variety), and in those cases characterized by full habit and high arterial tension, the drug has often been employed to advantage.

Pains which are paroxysmal in character yield best to acetanilid. It quiets the excitement in mania a potu, and frequently lessens the paroxysms of whooping-cough.

In doses of 3 to 5 grains (0.2-0.032 Gm.), thrice daily, acetanilid has proved efficient as a relief for seasickness. It has also been found serviceable in traumatic tetanus, purely to quiet the nervous symptoms.

The author has found it to be of great value in influenza, or "la grippe," combined or given alternately with salol, aspirin, or sodium salicylate.

Contraindications. - In low fevers, at any rate, not in repeated doses; in fatty or dilated heart, blood disorders, advanced tubercular disease, and exhaustion from hemorrhages.

Administration. - It may be prescribed in powders, pills, compressed tablets, capsules, or alcoholic solution. A speedier effect is produced if it is taken dissolved in a small quantity of alcohol or wine diluted with water.

The average dose as an antipyretic usually should not exceed 5 grains (0.3 Gm.); as an anodyne, 2 to 5 grains (0.1-0.3 Gm.). It may be repeated at intervals of about four hours or less, according to its effects.