Source and Composition. Antipyrin is a synthetical base, which forms salts analogous to those of Ammonium, and is a product of the destructive distillation of coal tar, though it may also be prepared synthetically. It has the formula C20H18N4O2—and the chemical name Dimethlyphenyl-pyrazolon. In the British pharmacopoeia it has the title Phenazone.
Characteristics. It occurs as a whitish, crystalline powder, which combines with acids to form salts, is somewhat bitter, and soluble in one-half its weight of hot water, and in its own weight of cold water; but is still more so if the water is acidulated with dilute nitro-hydrochloric acid. It is less soluble in alcohol, chloroform or ether, gives an intensely red color with Ferric Chloride, and a beautiful green with Nitric Acid. It is not irritant to either the stomach or the tissues, and may be administered hypodermically.
Dose and Administration. An average adult dose is about gr. x, which for antipyretic effect may be repeated hourly for 3 doses. For children, gr. ¼ per year of age between 2 and 5, gr. ½ per year from 5 to 10, not exceeding gr. v at a dose for any child under 15. If vomiting result, the same dose may be dissolved in half its weight of hot water, and injected hypodermically while warm.
Antipyrin has but little flavor, is not unpleasant, and is therefore readily taken by children, in which respect it is greatly superior to quinine. It may be administered in compressed tablets, each having 3, 5 or 10 grains.
Preparations. The only important salt is—
- *Antipyrini Salicylas, Antipyrin Salicylate, (Salipyrin),—formed by combining Salicylic Acid 57.7 and Antipyrin 42.3; a white, crystalline, odorless powder, very soluble in alcohol, insoluble in water. Its claims to preference are based upon its comparative harmlessness (ʒijss having been taken within 3 or 4 hours without the slightest ill effect); also its freedom from unpleasant after-results. Dose, gr. x-xxx every hour or 2 hours until ʒij have been taken.
Analogues of Antipyrin.
- *Chinolinum, Chinolin, C9H7N,—is a constituent of coal tar, but may be obtained from Quinine or Cinchonine by destructive distillation, or prepared artificially from Anilin or Nitrobenzol. It is a powerful antiseptic and antipyretic, closely resembling Quinine in its action, but of very disagreeable taste and odor. In moderate doses it lowers the pulse-rate and reduces the body-temperature; in large ones it diminishes reflex excitability, and causes dyspnoea, paralysis and collapse. It has been used in typhoid fever, acute rheumatism and erysipelas, also in typhus, diphtheria, etc., with varying success. In the latter disease, a 5 per cent. solution in weak alcohol is painted over the affected surface with great benefit. The Tartrate has been used with benefit in neuralgia and whooping- cough, and as an antiperiodic in intermittents. Dose of the Tartrate, gr. v-xx, in aqueous solution.
- *Kairinum, Kairin, C10H13NO.HCl.H2O,—is the Hydrochlorate of Oxyethyl-chinolin-hydride, an artificial substance prepared from Chinolin; occurring as a white, crystalline powder, freely soluble in water, but is best administered in wafer-paper or in capsule. It is a powerful antipyretic, producing however profuse sweating and vomiting; a severe rigor ushering in the subsequent rise of temperature, when its influence has worn off. In some cases of typhus it has caused cyanosis and collapse, but has not proven fatal, though 220 doses have been given in one case. It stains the urine a deep green color. By many authorities this drug is considered the most certain, most powerful and most rapid antipyretic which we possess,—but it has not been employed to any great extent since the advent of Antipyrin. Dose, gr. iij-gr. xxx. As antipyretic, gr. viij hourly for four doses, or until 100° F. is reached, then gr. iv, hourly during the period of defervescence.
- *Thallinum, Thallin (Parachinanisols),—has the chemical name Tetrahydro-paramethyl-oxychinolin, and is a synthetically prepared substance, occurring as a colorless powder, soluble in water, and forming salts with acids, of which the Sulphate is the most eligible. It is an antipyretic of very great power, but induces profuse sweating and a dangerous degree of depression. Dose, gr. ij-x, in tablets; a mean average dose being about gr. v.
Physiological Action. Antipyrin is a powerful antipyretic, a local anaesthetic and a general analgesic, and also possesses diaphoretic, mydriatic, antiseptic, disinfectant and slightly hypnotic powers. After the ingestion of a full medicinal dose, (gr. xx-xxx), there is a stimulant stage of short duration, in which the heart's action is increased, and a subjective sense of heat is experienced, with flushing of the face. This is soon followed by profuse sweating, coldness of the surface, slowed pulse, considerable depression, and if fever be present by lowered temperature; the latter coming on within half an hour after taking the drug and its degree being in direct ratio to the quantity administered, as also its continuance,—the former being usually from 3 to 5 degrees, and the latter from 1 to 10 hours, a fair average being about 2 hours. In one case a fall of 12° F. was observed. When given with Kairin, the mixture of the two drugs has been found to produce a much greater fall of temperature, with longer continuance down, than that produced by an equal quantity of either drug given alone. After the antipyretic effect of the dose has passed off, the temperature (in fever) commences to rise again,—the onset being usually preceded by a chill, which is of slight degree when compared with the severe rigors and dangerous depression occurring under the action of Kairin, Chinolin, and other members of the group.
In health its administration gives rise to slight nausea, singing in the ears, and a reduction of the body temperature of scarcely any extent, about 1/10° F. It slightly raises the arterial tension and blood-pressure;—sometimes (but seldom) induces vomiting, also a peculiar eruption on the skin;—and (very rarely) such a degree of depression as to amount to collapse. It has no effect upon the respiration, but acts as a sedative upon the cerebrum, leaving behind a somewhat depressant influence on the brain. It dilates the pupils and is eliminated by the kidneys, appearing in the urine some three hours after its ingestion. The profuse sweating which it causes may be prevented by giving in advance a small dose of Atropine or Agaricine. In toxic dose its principal influence is exerted upon the blood, altering the shape of the red corpuscles, separating the hematin, and causing decomposition of that fluid.
As an Antipyretic, Antipyrin, like Alcohol, acts by a double mode of operation,—(1) by diminishing oxidation, and (2) by promoting heat-loss. The latter is attained by dilating the cutaneous vessels, allowing free radiation from the surface, and by the refrigerant action of the evaporation of the sweat. As an Analgesic, Antipyrin has a very considerable degree of power, in common with all the Chinolin derivatives; but its property in this respect is found to act almost entirely upon pain due to manifestations of the rheumatic diathesis. In general anodyne action, it is not to be compared with the derivatives of Opium. Its hemostatic power is claimed to be superior to that of Ergotine.
Therapeutics. One of the most popular of the modern antipyretics, Antipyrin deserves its high rank, being one of the most certain depressants of pyrexia, though somewhat dangerous, and at the same time being devoid of any other influence upon the course of any febrile disorder. Its principal applications are as follows, viz.:—
- In Hyperpyrexia from any cause, it is efficient.
- Acute Rheumatism,—it has held the first place as a remedy, for some time; a claim which is now disputed in favor of Salol. In this affection Salipyrin has been used with much satisfaction.
- Typhoid Fever and other febrile conditions, wherein hyperpyrexia occurs,—as phthisis, erysipelas, pleuritis, pneumonia, surgical fever, etc.
- Neuralgiae, Neuritis, and other painful affections, especially when of rheumatic origin, as lumbago, sciatica, hemicrania, supra-orbital neuralgia, etc.,—in which 10-grain doses are generally sufficient, and may be given hypodermically. Salipyrin is herein remarkably efficient.
- Painful Affections of hysterical persons; pain from cerebral tumors and from cardiac diseases, also painful menstruation;—all of which are promptly relieved by it in most cases.
- Influenza,—Salipyrin was extensively employed during the epidemic of 1891, and was highly extolled for its efficient action therein, as also for its freedom from cardiac disturbance.
A Compend of Materia Medica, Therapeutics, and Prescription Writing, 1902, by Sam'l O. L. Potter, M.D., M.R.C.P.L.