Acetanilidum

Acetanilid

Acetanilid (Antifebrin).—An acetyl derivative of aniline. The term antifebrin, by which acetanilid is best known, is a proprietary designation; acetanilid is a more scientific term, unrestricted in use, and hence should be preferred. Also, the name antifebrin expresses but one, and not the most important, of its powers.

Properties

Physical and Physiological. — Acetanilid is a white, crystallized powder, without odor, and having a slight, characteristic, but not disagreeable taste. It is soluble to some small extent in cold water, 1 part to 194; more soluble in warm water, 1 part to 50 of water at 105° Fahr.; and dissolving readily in alcohol (3·5), in ether (6), and in chloroform (7). Chemically, acetanilid is aniline, less an atom of hydrogen replaced by acetyle. The dose ranges between four and eight grains. The latter quantity need rarely be exceeded in a single dose, but a considerably larger amount can be safely administered in twenty-four hours. Drachm-doses have been taken by healthy persons without suffering. There are important differences in the action of moderate medicinal and of toxic doses (Weill), for the-effect of the latter on the blood-globules introduces a special pathogenic influence which must change the character of the symptoms produced.

Ordinary medicinal doses do not irritate the stomach, and indeed, as the author has observed, sometimes allay nausea. Notwithstanding its insolubility, acetanilid rapidly diffuses into the blood. The normal constituents of the blood are quickly changed in composition; the oxyhaemoglobin lessens in quantity, and a corresponding formation of methyhaemoglobin takes place. The effect of such changes is to seriously modify that function entitled the "ozonizing function," and to impair constructive tissue metamorphosis, and with it heat-production. The effect of full medicinal doses in this way is partly manifested in the cyanosis usually present, but, as no ill result occurs, it is certain that the change is only temporary. The reduction of temperature takes place only when fever is present, and no action follows the administration of the remedy during apyrexia. It results from this fact that, to obtain the fullest effect from acetanilid as an antipyretic, it should be given at the point of maximum elevation of temperature.

Acetanilid raises the intra-vascular blood-pressure, chiefly by contracting the peripheral arterioles, and thus increases the work of the heart. As the vascular tension rises, the heart-beats lessen in number, but gain in force After a time, as is the physiological law, the stimulation of the cardiac motor apparatus is succeeded by diminished action and irregularity of the rhythm—consequences of a protracted and powerful impression on the centers of reflex action, and of the vasomotor system. It is a curious fact that, in a considerable number of persons, only the effects on the nervous system are produced, and a decline of temperature and failure of respiration are not experienced. The mind continues clear, and vocal expression is not impaired, until the serious changes wrought in the blood bring about coma and insensibility. As the effects of the medicament are developed, the reflexes lessen, and the irritability of motor and sensory nerves and of the pneumogastric progressively declines. Analgesia and anaesthesia are products of its action, but it is evident that the interference in the respiratory function of the blood has much to do with the functional changes occurring in the nervous system.

In the beginning, acetanilid excites increased action in the central nervous apparatus, but, as the impression gains in force, a quantitative decline takes place in the functions of motility and sensibility, and ultimately they are suspended entirely. Large doses have so serious an effect on the red blood-globules that collapse follows a brief period of excitement. As the antipyretic power is due to the injury done to the "ozonizing function of the blood," as has been explained, it is clear that the therapeutical applications for diminishing fever-heat are not without danger, and, although it is an efficient remedy for this purpose, it is probably not safer when the proper dose is exceeded than the other antipyretics of the same character. It is true, to accomplish a given result, so small, comparatively, is the dose required, that it is not necessary to exhibit that quantity which will produce dangerous symptoms. In common with the antipyretics of this class, but far less frequently and severely, acetanilid causes sweating at the end of its impression, and a rigor as the temperature begins to rise again.

Opinions differ somewhat in regard to the certainty and the power of acetanilid as an antipyretic. Eisenhart, Riese, Krieger, and other German observers, find it to be extremely uniform in its effects on febrile heat; but Dujardin-Beaumetz holds that small doses will sometimes have a decided power to lessen the temperature, and, again, quite large doses will fail of effect. He regards it, therefore, as a rather capricious antipyretic, and hence inferior to antipyrin for this purpose, although threatening symptoms are but rarely induced by its therapeutical administration, with the exception of cyanosis, which occurs when the larger doses are given, but does not necessarily indicate an untoward action.

The amount required to produce distinct antipyretic effects ranges from four to eight grains, the latter dose having proved to be an effective quantity for lessening fever-heat in general. A much larger quantity can be given with entire safety, if the circumstances demand the increase. Huber has administered from sixty to seventy grains, and from ninety to a hundred grains in twenty-four hours, without any ill effects. The reduction of temperature begins in one to two hours after the dose has been taken, and the effect is maintained for four to twelve hours.

Therapy

The applications of acetanilid to the treatment of diseases are based on its physiological actions. There are two directions in especial that its curative powers take: to lessen fever (antipyretic action); to diminish the functional activity of motor and sensory nerves, and to inhibit reflex actions.

As respects fever, when the high temperature must be reduced, acetanilid is effective, and although it may exert less power than an-tipyrin, has many advantages, in size of dose, ease of administration, and freedom from untoward effects. Its special field of utility is the relief of inflammatory conditions of nerves. In neuritis, the author has found it so effective that it has seemed to have specific action. The pains {neuralgia, myalgia, etc.) due to inflammation of nerves are, as a rule, soon relieved, and the dose for this purpose need not exceed three to five grains ter die. In optic neuritis, with pain, Du-jardin-Beaumetz finds it exceedingly effective, not only in removing the nerve-pain, but in arresting the inflammatory process on which the pain depends. Very admirable results have been had from acetanilid in the pains of locomotor ataxia. As all the world knows, these pains have not hitherto been at all readily relieved by the means available, and hence the importance of this recent contribution to our resources. The pains of herpes zoster, and of sciatica produced by local injury, have also been promptly arrested by this remedy, while no apprehension of a habit has intervened to lessen the satisfaction derived from its curative power.

To Lepine, of Lyons, to whom we owe the first knowledge of the curative power of acetanilid in the affections of the nervous system mentioned above, and to Dujardin-Beaumetz, we are also indebted for the suggestion of its use in epilepsy. The experiences and observations thus far accumulated do not warrant the statement of exact formula to guide the administration. That it lessens reflex excitability and opposes spasm is evident, but such an action does not include the whole of its powers. The impression made by acetanilid on the vaso-motor system must be taken into account as an element in its curative action. As it causes contraction of the arterioles, and slows somewhat the heart-beat, it must be more useful in those cases of epilepsy characterized by full habit, active circulation, redness of face, injection of the conjunctivae, etc., than in the anaemic, the pale and feeble. For similar considerations, it will prove more useful in diurnal than in nocturnal epilepsy, for, as in the state of sleep there is an anaemic condition of the brain, it is probable that an agent contributing to this will only increase the tendency to convulsions.

Exalgine

By this name a new remedy having valuable anodyne property has been introduced by Dujardin-Beaumetz and Bardet. It is a derivative of acetanilid with methyl, and hence the name, given to designate, not its composition, but its most important curative power. The chemical name is Orthomethylacetanilid, which is too difficult and unwieldy for general use. It has proved to be a highly effective remedy for neuralgia, and is free from ill effects. The dose required for internal exhibition in painful affections is determined by the degree of pain and the nature of the cause producing it. As a hypnotic it has proved to be one of the most effective, and this without any of the immediate and remote actions of a disagreeable kind.