Antipyrine

ANTIPYRINE, Antipyrinum (from Greek anti- against and pyr-fire, heat), C11H12N2O (synonyms: Pyrazolum phenyldimethylicum, Phenyl-dimethyl-isopyrazolum, Analgesinum, Anodynum and others), has two structural formulas: according to Knorr (Knorr-I) and according to Michaelis (Michaelis-II) as follows: N CO, ;; O ;;, CH3 C, (I), C6H5 (II). A. was obtained synthetically by Knorr in 1884 by condensation of phenylhydrazine with acetoacetic ester and was erroneously classified by Knorr as a derivative of quinoline; later it was found that the basis of A. is the pyrazole ring, from which phenylhydrazine does not detach and cannot, as such, act on the organism. A. is colorless, opaque tabular crystals with barely perceptible odor and slightly bitter taste; melts at t° 110-112°; soluble in 1 part water, in 1 part alcohol, in 1.5 parts chloroform, and in 80 parts ether. Highly diluted solutions of A. give with ferric chloride a dark red coloring, which turns yellow with sulfuric acid; with nitrous acid-green coloring; with tannic acid-a precipitate. Aqueous solutions of A. are of neutral reaction.

In therapy, A. was introduced by Filehne. Local action-irritating; when administered subcutaneously, it causes abscesses and tissue necrosis; when taken internally, nausea, vomiting, and stomach pains may occur. The local irritating effect on vessels explains its hemostatic action when applied as solutions (5-10%) to bleeding mucous membranes (nose, bladder, vagina); at the site of bleeding cessation: narrowing of vessels, decrease in mucus secretion, reduction in painful sensations. The general action of small (0.5-1.0) therapeutic doses of A. on the central nervous system is expressed in a peculiar state of some stupor, due to which pain and reflex excitability decrease and general calmness sets in. Heart rate increases slightly; breathing does not change; the vasomotor center is depressed, with skin vessels predominantly dilating, while internal ones remain almost unchanged. It has been noted that A. dilates vessels, not only by depressing the vasomotor center, but also by acting on the vessel walls themselves.

The amount of urine increases; urine is red or reddish-brown color. About 15-20 minutes after taking A., the temperature of feverish patients begins to decrease, falling to normal or lower. After remaining decreased for 2-6 hours, the temperature rises again, but with repeated use of A., the temperature decrease becomes more persistent (10-12 hours). A. lowers the temperature more strongly in patients with remittent or intermittent types of fever. In septic and pyemic diseases, however, the temperature does not fall as much from A. Often the decrease in temperature from A. is accompanied by increased sweating, and when the temperature rises, chills are observed. The cause of the antipyretic action of A. is considered to be increased heat loss from the body due to dilation of skin vessels and increased blood supply to them; increased sweating promotes heat loss. Heat production in feverish patients from A. does not change (Kumagawa's research on nitrogen metabolism) or may even increase (Suzilovsky, Maragliano), but the temperature still decreases, because heat loss exceeds heat production; such a ratio is the result of A.'s action on the temperature-regulating center, which copes well with the action of A. in healthy individuals: in the latter, the temperature does not fall even with much larger doses (2.0 - 4.0) than in patients, and decreases only with large toxic doses of A.

A. is excreted from the body mostly unchanged, and partly in combination with sulfuric and glucuronic acids. Side effects of A. are diverse but pass quickly; the most common include: skin rashes-erythema, roseola, urticaria, scarlet redness; profuse sweating, sometimes leading to collapse in weak, cardiac, pneumonia, and tuberculosis patients; nausea, vomiting, intestinal disorders; dizziness, ringing in the ears, visual impairment; catarrhs of mucous membranes and others. Simultaneous administration of A. with calomel to a patient can cause very dangerous poisoning, because these substances react with each other in an alkaline medium and from them a poisonous metalloorganic compound is formed (Paderi).

Therapeutic use of A.: in febrile diseases as an antipyretic, analgesic, and sedative; in nervous disorders, neuralgia, headaches (migraines) as an analgesic and sedative; also for shooting pains in tabetics, during labor, insomnia, empirically-in diabetes insipidus and mellitus, in seasickness, chorea; as a local hemostatic-in nasal bleeding, bleeding during surgical procedures (lithotripsy). Maximum single dose of A.-2.0, daily-6.0.

For detection of A. in forensic cases, the objects under examination (internal organs, vomit, intestinal contents, etc.) are treated with an alkaline solution and A. is extracted with chloroform; from the filtered extract, chloroform is distilled off and pure A. is isolated by recrystallization, which is determined by color reactions. For quantitative determination, the A. solution is precipitated with a 1/20 solution of picric acid and the excess is titrated with a 1/10 solution of caustic soda (indicator-phenolphthalein).